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Purpose To quantify the defocus characteristics in the near‐work environment at home and investigate the relationship with subsequent myopia progression. Methods Fifty subjects (aged 7–12 years) were recruited and followed for 1 year. The home near‐work environment (writing desk) was measured at a baseline home‐visit using the Kinect‐for‐Windows to capture a 3‐dimensional image. The depth values of the image were then converted into scene defocus with respect to the subject’s viewpoint. The defocus characteristics were quantified as the dioptric volume (the total amount of net defocus, or DV) and standard deviation of the defocus values (SDD). Information on home size, time spent outdoors, and in front of a desk were also obtained. Univariate correlation, and multivariate regression were used to assess the association between myopia progression, defocus characteristics, and other co‐variates. Results The baseline spherical equivalent refraction (M) and refraction change over 1 year (∆M) were − 1.51 ± 2.02 D and − 0.56 ± 0.45 D respectively. DV was not significantly correlated with ∆M (Spearman’s ρ = −0.25, p = 0.08), while SDD was negatively correlated to ∆M (Spearman’s ρ = −0.42, p = 0.003). Although SDD was not a significant predictor in multivariate analysis, the regional DV at 15°–20° eccentricity was significant (p = 0.001). Home size (F 2,50 = 7.01, p = 0.002) and time spent outdoors (Independent t = −2.13, p = 0.04) were also associated with ∆M, but not time spent in front of desk (Independent t = 0.78, p = 0.44). Conclusion The defocus profile in the home environment within the para‐central field of view is associated with childhood refractive error development.

Systemic hypertension or hypertension is a very common chronic age-related disease worldwide. It is typically characterised by a sustained elevation of blood pressure, particularly when the systolic blood pressure and/or diastolic blood pressure are of more than 140 mmHg and 90 mmHg, respectively. If hypertension is not well controlled, it may lead to an increased risk of stroke and heart attack. It has been shown that hypertension is linked to various ocular diseases, including cataract, diabetic retinopathy, age-related macular degeneration, and glaucoma. Glaucoma is the leading cause of irreversible blindness worldwide. Primary open angle glaucoma is the most common form of the disease and is usually characterised by an increase in intraocular pressure. This condition, together with normal tension glaucoma, constitutes open angle glaucoma. Systemic hypertension has been identified as a risk factor for open angle glaucoma. It is speculated that blood pressure is involved in the pathogenesis of open angle glaucoma by altering intraocular pressure or ocular blood flow, or both. Recent evidence has shown that both extremely high and low blood pressure are associated with increased risk of open angle glaucoma. Additional pathogenic mechanisms, including increased inflammation likely to be involved in the development and progression of these two diseases, are discussed.

Our previous research showed that increased phosphorylation of connexin (Cx)36 indicated extended coupling of AII amacrine cells (ACs) in the rod-dominant mouse myopic retina. This research will determine whether phosphorylation at serine 276 of Cx35-containing gap junctions increased in the myopic chicken, whose retina is cone-dominant. Refractive errors and ocular biometric dimensions of 7-days-old chickens were determined following 12 h and 7 days induction of myopia by a −10D lens. The expression pattern and size of Cx35-positive plaques were examined in the early (12 h) and compensated stages (7 days) of lens-induced myopia (LIM). At the same time, phosphorylation at serine 276 (functional assay) of Cx35 in strata 5 (S5) of the inner plexiform layer was investigated. The axial length of the 7 days LIM eyes was significantly longer than that of non-LIM controls (P

Ischemia is a common pathological condition present in many neurodegenerative diseases, including ischemic stroke, retinal vascular occlusion, diabetic retinopathy, and glaucoma, threatening the sight and lives of millions of people globally. Ischemia can trigger excessive oxidative stress, inflammation, and vascular dysfunction, leading to the disruption of tissue homeostasis and, ultimately, cell death. Current therapies are very limited and have a narrow time window for effective treatment. Thus, there is an urgent need to develop more effective therapeutic options for ischemia-induced neural injuries. With emerging reports on the pharmacological properties of natural flavonoids, these compounds present potent antioxidative, anti-inflammatory, and antiapoptotic agents for the treatment of ischemic insults. Three major active flavonoids, baicalein, baicalin, and wogonin, have been extracted from Scutellaria baicalensis Georgi (S. baicalensis); all of which are reported to have low cytotoxicity. They have been demonstrated to exert promising pharmacological capabilities in preventing cell and tissue damage. This review focuses on the therapeutic potentials of these flavonoids against ischemia-induced neurotoxicity and damage in the brain and retina. The bioactivity and bioavailability of baicalein, baicalin, and wogonin are also discussed. It is with hope that the therapeutic potential of these flavonoids can be utilized and developed as natural treatments for ischemia-induced injuries of the central nervous system (CNS).

Purpose We analyzed the association between bedtime smart device usage habits and accelerometer-measured sleep outcomes (total sleeping time, sleep efficiency, and wake after sleep onset) in Hong Kong children and adolescents aged 8–14. Methods A total of 467 students in Hong Kong participated in this study from 2016 to 2017. They self-reported their bedtime smart device usage habits. The primary caregiver of each participant was also invited to complete a self-administered questionnaire about the family’s social-economic status and bedtime smart device usage habits. An ActiGraph GT3X accelerometer was used to assess participants’ 7-day sleep outcomes. Results The mean age of the participants was 10.3 (SD 1.9), and 54% were girls. Among the participants, 27% (n = 139) used a smart device before sleep, and 33% (n = 170) kept the smart device on before sleep. In total, 27% (n = 128) placed the smart device within reach before sleep, 23% (n = 107) would wake up when notifications were received, and 25% (n = 117) immediately checked the device after being awakened by a notification. Multiple regression controlling for age, sex, socio-economic status, and other confounders showed that those who woke up after receiving a notification had a statistically longer sleeping time (19.7 min, 95% CI: 0.3, 39.1, p = 0.046), lower sleep efficiency (− 0.71%, 95% CI − 1.40, − 0.02, p = 0.04), and a longer wake after sleep onset (2.6 min, 95% CI: 0.1, 5.1, p = 0.045) than those who did not. Nonetheless, all primary caregivers’ bedtime smart device habits were insignificantly associated with all sleep outcomes of their children. Conclusion Those who woke up after receiving smart device notifications had lower sleep efficiency and longer wake after sleep onset than those who did not, and they compensated for their sleep loss by lengthening their total sleep time.

Uncorrected refractive errors can lead to permanent debilitating eye conditions if not corrected in a timely manner. Contemporary diagnostic methods rely on the professional acumen of optometrists and the use of expensive devices, which may not be easily accessible to all. According to the optical principle of photorefraction, refractive error can be estimated based on a relative pupil and crescent size of an eye image taken by a camera from a specified working distance. A low-cost approach would be to leverage smartphones with cameras for this purpose. However, the poor image quality generated from basic smartphones poses a challenge for the current approach as they often fail to accurately distinguish the crescent from the iris. We propose a novel method to detect and accurately measure the iris and crescent from smartphone photos. Based on this method, we further propose a set of features for machine learning to build our refractive error estimation model. The performance of our models are evaluated in an in-depth experiment.

This study examined the association between smart device usage and the 1-year change in refractive error among a representative sample of Hong Kong children and adolescents aged 8&ndash, 14 years. A total of 1597 participants (49.9% male, mean age 10.9, SD 2.0) who completed both baseline (2017&ndash, 2018) and 1-year follow-up (2018&ndash, 2019) eye examinations were included in the present study. The non-cycloplegic auto-refractive error was measured and the average spherical equivalent refraction (SER) was analyzed. The participants also self-reported their smart device usage at baseline. Multivariate regression adjusted for age, sex, baseline SER, parents&rsquo, short-sightedness, BMI, time spent on moderate-to-vigorous physical activity (MVPA), and caregiver-reported socio-economic status showed that, compared with the reference group (&lt, 2 hours per day on both smartphone and tablet usages), those who spent &ge, 2 hours per day using a smartphone and &lt, 2 hours per day using a tablet had a significantly negative shift in refractive error (1-year change in SER &minus, 0.25 vs. &minus, 0.09 D, p = 0.01) for the right eye, while the level of significance was marginal (1-year change &minus, 0.28 vs. &minus, 0.15 D, p = 0.055) for the left eye. To conclude, our data suggested spending at most 2 hours per day on both smartphones and tablets.

Refractive errors, such as myopia and astigmatism, can lead to severe visual impairment if not detected and corrected in time. Traditional methods of refractive error diagnosis rely on well-trained optometrists operating expensive and importable devices, constraining the vision screening process. Advance in smartphone camera has enabled novel low-cost ubiquitous vision screening to detect refractive error or ametropia through eye image processing, based on the principle of photorefraction. However, contemporary smartphone-based methods rely heavily on hand-crafted features and sufficiency of well-labeled data. To address these challenges, this paper exploits active learning methods with a set of Convolutional Neural Network features encoding information of human eyes from pre-trained gaze estimation model. This enables more effective training on refractive error detection models with less labeled data. Our experimental results demonstrate the encouraging effectiveness of our active learning approach. The new set of features is able to attain screening accuracy of more than 80% with mean absolute error less than 0.66, meeting the expectation of optometrists for 0.5 to 1. The proposed active learning also requires significantly fewer training samples of 18% in achieving satisfactory performance.

Glaucoma, a form of progressive optic neuropathy, is the second leading cause of blindness worldwide. Being a prominent disease affecting vision, substantial efforts are being made to better understand glaucoma pathogenesis and to develop novel treatment options including neuroprotective and neuroregenerative approaches. Cell transplantation has the potential to play a neuroprotective and/or neuroregenerative role for various ocular cell types (e.g., retinal cells, trabecular meshwork). Notably, glaucoma is often associated with elevated intraocular pressure, and over the past 2 decades, several rodent models of chronic ocular hypertension (COH) have been developed that reflect these changes in pressure. However, the underlying pathophysiology of glaucoma in these models and how they compare to the human condition remains unclear. This limitation is the primary barrier for using rodent models to develop novel therapies to manage glaucoma and glaucoma-related blindness. Here, we review the current techniques used to induce COH-related glaucoma in various rodent models, focusing on the strengths and weaknesses of the each, in order to provide a more complete understanding of how these models can be best utilized. To so do, we have separated them based on the target tissue (pre-trabecular, trabecular, and post-trabecular) in order to provide the reader with an encompassing reference describing the most appropriate rodent COH models for their research. We begin with an initial overview of the current use of these models in the evaluation of cell transplantation therapies.

The molecular pathophysiology of corticosteroid-induced ocular hypertension (CIH) is not well understood. To determine the biological mechanisms of CIH, this study investigated protein expression profiles of human trabecular meshwork (hTM) cells in response to dexamethasone and prednisolone treatment. Both discovery-based sequential windowed data independent acquisition of the total high-resolution mass spectra (SWATH-MS) and targeted based high resolution multiple reaction monitoring (MRM-HR) confirmation were applied using a hybrid quadrupole-time-of-flight mass spectrometer. A comprehensive list of 1759 proteins (1% FDR) was generated from the hTM. Quantitative proteomics revealed 20 differentially expressed proteins (p-value ≤ 0.05 and fold-change ≥ 1.5 or ≤ 0.67) commonly induced by prednisolone and dexamethasone, both at 300 nM. These included connective tissue growth factor (CTGF) and thrombospondin-1 (THBS1), two proteins previously implicated in ocular hypertension, glaucoma, and the transforming growth factor-β pathway. Their gene expressions in response to corticosteroids were further confirmed using reverse-transcription polymerase chain reaction. Together with other novel proteins identified in the data sets, additional pathways implicated by these regulated proteins were the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway, integrin cell surface interaction, extracellular matrix (ECM) proteoglycans, and ECM-receptor interaction. Our results indicated that an integrated platform of SWATH-MS and MRM-HR allows high throughput identification and confirmation of novel and known corticosteroid-regulated proteins in trabecular meshwork cells, demonstrating the power of this technique in extending the current understanding of the pathogenesis of CIH.

Purpose People in Hong Kong generally live in a densely populated area and their homes are smaller compared with most other cities worldwide. Interestingly, East Asian cities with high population densities seem to have higher myopia prevalence, but the association between them has not been established. This study investigated whether the crowded habitat in Hong Kong is associated with refractive error among children. Methods In total, 1075 subjects [Mean age (S.D.): 9.95 years (0.97), 586 boys] were recruited. Information such as demographics, living environment, parental education and ocular status were collected using parental questionnaires. The ocular axial length and refractive status of all subjects were measured by qualified personnel. Results Ocular axial length was found to be significantly longer among those living in districts with a higher population density (F2,1072 = 6.15, p = 0.002) and those living in a smaller home (F2,1072 = 3.16, p = 0.04). Axial lengths were the same among different types of housing (F3,1071 = 1.24, p = 0.29). Non-cycloplegic autorefraction suggested a more negative refractive error in those living in districts with a higher population density (F2,1072 = 7.88, p

To examine the difference between primary and secondary retinal ganglion cell (RGC) degeneration, the protein expression at four regions of retina including superior, temporal, inferior and nasal quadrant in a rat model of partial optic nerve transection (pONT) using 2‑D Fluorescence Difference Gel Electrophoresis (DIGE) were investigated. Unilateral pONT was performed on the temporal side of optic nerves of adult Wistar rats to separate primary and secondary RGC loss. Topographical quantification of RGCs labeled by Rbpms antibody and analysis of axonal injury by grading of optic nerve damage at 1 week (n=8) and 8 weeks (n=15) after pONT demonstrated early RGC loss at temporal region, which is considered as primary RGC degeneration and progressing RGC loss at nasal region, which is considered as secondary RGC degeneration. Early protein expression in each retinal quadrant (n=4) at 2 weeks after pONT was compared with the corresponding quadrant in the contralateral control eye by DIGE. For all comparisons, 24 differentially expressed proteins (>1.2‑fold; P

Rho-associated coiled coil-forming protein kinase (ROCK) inhibitors represent a novel class of anti-glaucoma drugs because of their ocular hypotensive effects. However, the underlying mechanisms responsible for lowering intraocular pressure (IOP) are not completely clear. The protein profile changes in primary human trabecular meshwork (TM) cells after two days treatment with a ROCK inhibitor were studied using label-free SWATH acquisition. These results provided significant data of key protein candidates underlying the effect of ROCK inhibitor. Using the sensitive label-free mass spectrometry approach with data-independent acquisition (SWATH-MS), we established a comprehensive TM proteome library. All raw data generated from IDA and SWATH acquisitions were uploaded and published in the Peptide Atlas public repository (http://www.peptideatlas.org/) for general release (Data ID PASS01254).

In this subject, we aim to integrate community services with students’ learning opportunities. Students work in groups and organize and implement a vision screening project by themselves under supervision. Through this subject, students are given opportunities to act upon their roles as community service providers, care, work, and communicate with various disciplines to bridge together knowledge they have acquired during their university studies and then share and apply their special interests with others. The project not only benefits service users, but also provides a very structured learning environment for students to gain experience working with a number of people in different levels of the community and to better understand societal needs, especially in this major public health concern of blindness prevention.

Background: Elevated levels of nitric oxide (NO  ), a pro-oxidant that has been associated with numerous retinal diseases, have been implicated in experimental glaucoma models. This study investigated the oxidative effects of sodium nitroprusside (SNP), a nitric oxide donor, on the retinal lipids and proteins and evaluated the potential protective effects of glutathione (GSH). Methods: Porcine retinal homogenates were incubated with 0, 1, 2, 3, 4 and 5 lM SNP. Malondialdehyde (MDA) levels were assayed spectrophotometrically to quantify lipid peroxidation. Differential protein expressions of 3 lM SNP-treated retinal homogenates were compared with controls after the conduction of twodimensional gel electrophoresis. Mass spectrometric data was used to identify proteins in NCBInr database. Furthermore, GSH was co-incubated with 3 lM SNP-treated retinal homogenates. MDA levels and protein expressions were compared with SNP-treated controls. Results: SNP significantly increased retinal-MDA levels (p = 0.0002). 2-D gel electrophoresis images displayed a significant change in 13 protein spot expressions (p < 0.05). GSH suppressed SNP-induced MDA elevation (p < 0.0001) and selected protein changes (p < 0.05). SNP down-regulated paraoxonase/arylesterase 2 precursor (PON2), b-actin and b-tubulin; however, these effects were prevented by a co-incubation with GSH, as confirmed by Western blots. Conclusions: Nitric oxide induced lipid and protein changes in retinal tissues. The effects were partially reversed by co-incubation with GSH. Data from this study suggests that nitric oxide-induced retinal oxidative stress induces specific molecular changes. This may enable us to better understand the pathogenesis of glaucoma. Further studies are indicated to explore potential pharmacological applications of GSH in nitric oxide-related retinal diseases.

Purpose To investigate the effects of cAMP on transepithelial electrical parameters and fluid transport across porcine ciliary epithelium. Methods Transepithelial electrical parameters were determined by mounting freshly isolated porcine ciliary epithelium in a modified Ussing chamber. Similarly, fluid movement across intact ciliary body was measured with a custom-made fluid flow chamber. Results Addition of 1, 10, and 100 μM 8-Br-cAMP (cAMP) to the aqueous side (nonpigmented ciliary epithelium, NPE) induced a sustained increase in short-circuit current (Isc). Addition of niflumic acid (NFA) to the aqueous surface effectively blocked the cAMP-induced Isc stimulation. The administration of cAMP to the stromal side (pigmented ciliary epithelium, PE) triggered a significant stimulation of Isc only at 100 μM. No additive effect was observed with bilateral application of cAMP. Likewise, forskolin caused a significant stimulation of Isc when applied to the aqueous side. Concomitantly, cAMP and forskolin increased fluid transport across porcine ciliary epithelium, and this stimulation was effectively inhibited by aqueous NFA. Depleting Cl- in the bathing solution abolished the baseline Isc and inhibited the subsequent stimulation by cAMP. Pretreatment with protein kinase A (PKA) blockers (H89/KT5720) significantly inhibited the cAMP- and forskolin-induced Isc responses. Conclusions Our results suggest that cAMP triggers a sustained stimulation of Cl- and fluid transport across porcine ciliary epithelium; Cl- channels in the NPE cells are potentially a cellular site for this PKA-sensitive cAMP-mediated response.

We present a vision-based, data-driven approach to identifying and measuring refractive errors in human subjects with low-cost, easily available equipment and no specialist training. Vision problems, such as refractive error (e.g. nearsightedness, astigmatism, etc) are common ocular problems, which, if uncorrected, may lead to serious visual impairment. The diagnosis of such defects conventionally requires expensive specialist equipment and trained personnel, which is a barrier in many parts of the developing world. Our approach aims to democratize optometric care by utilizing the computational power inherent in consumer-grade devices and the advances made possible by multimedia computing. We present results that show our system is able to match and outperform state-of-the-art medical devices under certain conditions.

Experimental evidence has shown that myopic and hyperopic optical defocus induces thickening and thinning of the choroids, respectively, moving the retina forward and backward toward the plane of focus; however, the underlying mechanism of this phenomenon remains elusive. It has been hypothesised that the change in choroidal thickness might be elicited by the alteration of ion and fluid transport across the retinal pigment epithelium (RPE). Therefore, the aims of the present study were to determine the content of specific Cl(-) transporter/channel mRNA and proteins in chick RPE in a normal, untreated state and in lens-induced myopia.Thirty-five White Leghorn chicks were used. Lens-induced myopia was achieved by securing a -10 D lens in one eye, while the control eye was mounted with a plano lens. The mRNA and protein expression of the targeted Cl(-) transporter and channels were assessed by real-time polymerase chain reaction and western blot, respectively.Our results showed that the gene and protein products of several Cl(-) transporter and channels including NKCC, CFTR, ClC-2, ClC-5, ClC-7 and CLCA were expressed in young chick RPE. After one day of -10 D lens wear, in addition to the myopic shift in refraction and choroidal thinning, there was a parallel reduction in content of some mRNAs and proteins (for example, NKCC) in the myopic eye compared with the fellow eye. Spontaneous recovery of these mRNAs and proteins to control levels was demonstrated after four days of treatment.The relative reduction of Cl(-) transporter and channel expression in the myopic eye might cause a decrease in ion and fluid transport across the RPE, leading to a thinning of the choroid and potentially accelerating axial elongation. Understanding of the identity of the Cl(-) transport machinery used in developing lens-induced myopia might facilitate development of novel approaches for controlling myopic progression by influencing fluid transport by the RPE.

The purpose of the study was to determine whether novel, selective antagonists of human A 3 adenosine receptors (ARs) derived from the A 3 -selective agonist Cl-IB-MECA lower intraocular pressure (IOP) and act across species. IOP was measured invasively with a micropipette by the Servo-Null Micropipette System (SNMS) and by non-invasive pneumotonometry during topical drug application. Antagonist efficacy was also assayed by measuring inhibition of adenosine-triggered shrinkage of native bovine nonpigmented ciliary epithelial (NPE) cells. Five agonist-based A 3 AR antagonists lowered mouse IOP measured with SNMS tonometry by 3–5 mm Hg within minutes of topical application. Of the five agonist derivatives, LJ 1251 was the only antagonist to lower IOP measured by pneumotonometry. No effect was detected pneumotonometrically over 30 min following application of the other four compounds, consonant with slower, smaller responses previously measured non-invasively following topical application of A 3 AR agonists and the dihydropyridine A 3 AR antagonist MRS 1191. Latanoprost similarly lowered SNMS-measured IOP, but not IOP measured non-invasively over 30 min. Like MRS 1191, agonist-based A 3 AR antagonists applied to native bovine NPE cells inhibited adenosine-triggered shrinkage. In summary, the results indicate that antagonists of human A 3 ARs derived from the potent, selective A 3 agonist Cl-IB-MECA display efficacy in mouse and bovine cells, as well. When intraocular delivery was enhanced by measuring mouse IOP invasively, five derivatives of the A 3 AR agonist Cl-IB-MECA lowered IOP but only one rapidly reduced IOP measured non-invasively after topical application. We conclude that derivatives of the highly-selective A 3 AR agonist Cl-IB-MECA can reduce IOP upon reaching their intraocular target, and that nucleoside-based derivatives are promising A 3 antagonists for study in multiple animal models.

Intraocular pressure (IOP) is regulated by the resistance to outflow of the eye's aqueous humor. Elevated resistance raises IOP and can cause glaucoma. Despite the importance of outflow resistance, its site and regulation are unclear. The small size, complex geometry, and relative inaccessibility of the outflow pathway have limited study to whole animal, whole eye, or anterior-segment preparations, or isolated cells. We now report measuring elemental contents of the heterogeneous cell types within the intact human trabecular outflow pathway using electron-probe X-ray microanalysis. Baseline contents of Na+, K+, Cl−, and P and volume (monitored as Na+K contents) were comparable to those of epithelial cells previously studied. Elemental contents and volume were altered by ouabain to block Na+-K+-activated ATPase and by hypotonicity to trigger a regulatory volume decrease (RVD). Previous results with isolated trabecular meshwork (TM) cells had disagreed whether TM cells express an RVD. In the intact tissue, we found that all cells, including TM cells, displayed a regulatory solute release consistent with an RVD. Selective agonists of A1 and A2 adenosine receptors (ARs), which exert opposite effects on IOP, produced similar effects on juxtacanalicular (JCT) cells, previously inaccessible to functional study, but not on Schlemm's canal cells that adjoin the JCT. The results obtained with hypotonicity and AR agonists indicate the potential of this approach to dissect physiological mechanisms in an area that is extremely difficult to study functionally and demonstrate the utility of electron microprobe analysis in studying the cellular physiology of the human trabecular outflow pathway in situ.

The mouse eye displays unusually rapid intraocular pressure (IOP) responses to topically applied drugs as measured by the invasive servo-null micropipette system (SNMS). To learn if the time course reflected rapid drug transfer across the thin mouse cornea and sclera, we monitored a different parameter, pupillary size, following topical application of droplets containing 40 μM (0.073 μg) carbachol. No miosis developed from this low carbachol concentration unless the cornea was impaled with an exploring micropipette as used in the SNMS. We also compared the mouse IOP response to several purinergic drugs, measured by the invasive SNMS and non-invasive pneumotonometry. Responses to the previously studied non-selective adenosine-receptor (AR) agonist adenosine, the A 3 -selective agonist Cl-IB-MECA and the A 3 -selective antagonist MRS 1191 were all enhanced to varying degrees, in time and magnitude, by corneal impalement. We conclude that the thin ocular coats of the mouse eye actually present a substantial barrier to drug penetration. Corneal impalement with even fine-tipped micropipettes can significantly enhance entry of topically-applied drugs into the mouse aqueous humor, reflecting either direct diffusion around the tip or a more complex impalement-triggered change in ocular barrier properties. Comparison of invasive and non-invasive measurement methods can document drug efficacy at intraocular target sites even if topical drug penetration is too slow to manifest convincing physiologic effects in intact eyes.

Glaucoma is a common and severe aging eye disease which can cause permanent visual loss if untreated. One common strategy of glaucoma treatment is to lower the intraocular pressure (IOP) of the eye. So far, the pharmacologic reduction of IOP is the only proven intervention that can delay the progression of glaucomatous damage. Lowering the IOP can be achieved either by reducing the rate of aqueous humor secretion or by facilitating the rate of aqueous drainage. The formation of aqueous humor is driven primarily by vectorial ion transport, mainly Cl–, across the ciliary epithelium from ciliary stroma into the posterior chamber, resulting in the generation of an osmotic gradient which drives water movement. Many ion transporters and channels have been shown to participate in the process of aqueous secretion. Among several other signaling mechanisms, the nitric oxide (NO) signaling cascade is thought to regulate the ion transport across the ciliary epithelium, thereby reducing the rate of aqueous humor formation and IOP. Therefore, in this review, the potential significance of NO in the regulation of aqueous humor formation and IOP will be discussed.

The eye’s aqueous humor is secreted by a bilayered ciliary epithelium comprising pigmented (PE) and nonpigmented (NPE) epithelial cell layers. Stromal Cl−enters the PE cells and crosses gap junctions to the NPE cells for release into the aqueous humor. Maxi-Cl−channels are expressed in PE cells, but their physiological significance is unclear. To address this question, excised patches and whole native bovine PE cells were patch clamped, and volume was monitored by calcein fluorescence. In symmetrical 130 mM NaCl, cAMP at the cytoplasmic surface of inside-out patches produced concentration-dependent activation of maxi-Cl−channels with a unitary conductance of 272 ± 2 pS ( n = 80). Voltage steps from 0 to ±80 mV, but not to ±40 mV, produced rapid channel inactivation consistent with the typical characteristics of maxi-Cl−channels. cAMP also activated the maxi-Cl−channels in outside-out patches. In both cases, maxi-Cl−channels were reversibly inhibited by SITS and 5-nitro-2-(phenylpropylamino)benzoate (NPPB). Decreasing cytoplasmic Cl−concentration reduced both open-channel probability and unitary conductance. Similarly, the membrane-permeant 8-bromo-cAMP stimulated outward and inward whole cell currents; the stimulation was larger at higher intracellular Cl−concentration. As with unitary currents, cAMP-triggered whole cell currents displayed inactivation at ±80 but not at ±40 mV. Moreover, cAMP triggered NPPB-sensitive shrinkage of PE cells. The results suggest that cAMP directly activates maxi-Cl−channels of native PE cells that contribute to Cl−release particularly from Cl−-loaded cells. These cAMP-activated channels provide a potential mechanism for reducing and modulating net aqueous humor secretion by facilitating Cl−reabsorption into the ciliary stroma.

Background There is currently limited information about ethnic differences in myopia prevalence within mainland China, especially in rural or semi-rural areas. We examined the prevalence of refractive errors, visual impairment and spectacle coverage in school children of varying ethnicity in Turpan, Xinjiang province. Methods A community eye care service was provided for five schools. Presenting monocular distance and near visual acuity (VA), and ocular alignment were assessed. Retinoscopy and cycloplegic subjective refraction were performed for participants with presenting visual impairment (distance VA worse than 0.3 logMAR; Snellen 6/12 or 20/40) or abnormal binocular vision. Questionnaires administered prior to the eye examinations were used to collect information regarding personal lifestyle and parental myopia. Results A total of 646 out of 690 (94%) subjects aged four to 19 years (11.9 ± 2.6; mean ± S.D.) completed the eye examination. Three hundred and eighty-two (59%) of participants were of Uyghur ethnicity, followed by Han, 176 (27%) and Hui, 74 (12%). The mean age of Uyghur, Han and Hui students was 12.3 ± 2.7, 11.4 ± 2.6 and 11.4 ± 2.3 years respectively, in which the Uyghur students were significantly older than the Han and Hui students (F(3,631) = 5.58 p Hui > Uyghur). As reported previously, uncorrected/under-corrected refractive error was the main cause of presenting visual impairment.

Ocular diseases such as cataract, glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy are the leading causes of blindness. The elderly population is at particular risk of developing one or more of these age-related ocular diseases. By virtue of multiple bioactivities, effort has been made to develop dietary flavonoids as complimentary therapies for ocular disorders. Dietary intake of flavonoids has been reported to reduce the risk of cataract and AMD. This review focuses on the main flavones baicalein, baicalin, and wogonin isolated from the Chinese medicinal herb, Scutellariae radix (SR), which has been widely used in Asian countries for the treatment of many diseases. Interest in SR has grown recently following new findings that suggest multiple routes of therapeutic action. This review will summarize the diverse pharmacological properties, therapeutic roles, and mechanisms of these flavones of SR in cellular and animal models of ocular diseases.

The possible existence of transepithelial bicarbonate transport across the isolated bovine ciliary body was investigated by employing a chamber that allows for the measurement of unidirectional, radiolabeled fluxes of CO2 + HCO[Formula: see text]. No net flux of HCO[Formula: see text] was detected. However, acetazolamide (0.1 mM) reduced the simultaneously measured short-circuit current ( I sc). In other experiments in which36Cl− was used, a net Cl− flux of 1.12 μeq · h−1 · cm−2 (30 μA/cm2) in the blood-to-aqueous direction was detected. Acetazolamide, as well as removal of HCO[Formula: see text] from the aqueous bathing solution, inhibited the net Cl− flux and I sc. Because such removal should increase HCO[Formula: see text] diffusion toward the aqueous compartment and increase the I sc, this paradoxical effect could result from cell acidification and partial closure of Cl−channels. The acetazolamide effect on Cl− fluxes can be explained by a reduction of cellular H+ and HCO[Formula: see text] (generated from metabolic CO2production), which exchange with Na+ and Cl−via Na+/H+ and Cl−/HCO[Formula: see text] exchangers, contributing to the net Cl− transport. The fact that the net Cl−flux is about three times larger than the I sc is explained with a vectorial model in which there is a secretion of Na+ and K+ into the aqueous humor that partially subtracts from the net Cl− flux. These transport characteristics of the bovine ciliary epithelium suggest how acetazolamide reduces intraocular pressure in the absence of HCO[Formula: see text] transport as a driving force for fluid secretion.

PURPOSE Apolipoprotein A1 (ApoA1) has been shown to inhibit myopia development in chicks, but the underlying biological mechanism remains unknown. Because ApoA1 interacts with cyclic adenosine monophosphate (cAMP) in many cellular systems, we examined whether this interaction is important in myopia development. METHODS The nonmetabolizable cAMP analogue 8-Bromo-cAMP (8-Br-cAMP) was administered intravitreally to the right eyes of 8-day old chicks for 4 consecutive days. Control eyes received vehicle. Chicks in group 1 received 8-Br-cAMP (0.1 mM or 1 mM) and were fitted with -10 diopter (D) lenses on both eyes, whereas chicks in group 2 (0.1 mM 8-Br-cAMP) wore plano lenses over both eyes. The levels of retinal cAMP and ApoA1 were examined in another two groups of chicks wearing -10 D (group 3) and +10 D lenses (group 4) over their right eyes for 3 days, respectively (plano over left eyes). RESULTS The 8-Br-cAMP significantly inhibited development of lens-induced myopia (group 1: 0.1 mM versus vehicle: +1.71 ± 1.22 D versus -8.00 ± 2.19 D; 1 mM versus vehicle: +1.38 ± 1.34 D versus -9.96 ± 1.14 D, mean ± SEM, P < 0.01 for both); 1 mM, but not 0.1 mM 8-Br-cAMP increased expression of retinal ApoA1 levels in right eyes (P < 0.01). The 8-Br-cAMP had minimal effect on normal eye growth. Both retinal cAMP and ApoA1 levels were significantly increased only in hyperopic eyes (group 4). CONCLUSIONS The 8-Br-cAMP robustly inhibited development of lens-induced myopia. The increase in retinal ApoA1 observed in cAMP-treated and hyperopic eyes suggested a possible interplay between ApoA1 and cAMP in regulating eye growth.

� secretion HCO3 � secretion abstract Glaucoma is a leading cause of irreversible blindness worldwide. Lowering intraocular pressure (IOP) is the only strategy documented to delay the appearance and retard the progression of vision loss. One major approach for lowering IOP is to slow the rate of aqueous humor formation by the ciliary epithe- lium. As discussed in the present review, the transport basis for this secretion is largely understood. However, several substantive issues are yet to be resolved, including the integrated regulation of secretion, the functional topography of the ciliary epithelium, and the degree and significance of species variation in aqueous humor inflow. This review discusses species differences in net secretion, particularly of Cl � and HCO3 secretion. Identifying animal models most accurately mimicking aqueous humor formation in the human will facilitate development of future novel initiatives to lower IOP.

Glaucoma is a leading cause of irreversible blindness in the world (1). Primary openangle glaucoma (POAG) is the most common form of glaucoma and its onset, as well as progression, is often insidious, leading to significant visual loss before being clinically diagnosed. POAG is frequently associated with elevated intraocular pressure (IOP) of the eye. It is incurable at present, although its progression can be retarded by lowering the IOP by medication and/or surgery. If pharmacological agents fail to attain a targeted hypotensive response within the framework of the clinical characteristics and course, surgery will be indicated. The IOP is physiologically maintained within a relatively narrow range bracketing a mean of approximately 15 mmHg. The level of IOP reflects a dynamic balance between secretion (inflow) and drainage (outflow) of aqueous humor. The aqueous humor is a transparent fluid that is formed by the ciliary processes (epithelium) of the eye. After its production, aqueous humor flows from the posterior chamber to the anterior chamber of the eye via the pupil (Fig. 1). In the anterior chamber, the temperature difference between the warmer iris and the cooler cornea results in a convectional fluid circulation.

The aqueous humor is formed by the bilayered ciliary epithelium. The pigmented ciliary epithelium (PE) faces the stroma and the nonpigmented ciliary epithelium (NPE) contacts the aqueous humor. Cl(-) secretion likely limits the rate of aqueous humor formation. Many transport components underlying Cl(-) secretion are known. Cl(-) is taken up from the stroma into PE cells by electroneutral transporters, diffuses to the NPE cells through gap junctions and is released largely through Cl(-) channels. Recent work suggests that significant Cl(-) recycling occurs at both surfaces of the ciliary epithelium, providing the basis for modulation of net secretion. The PE-NPE cell couplet likely forms the fundamental unit of secretion; gap junctions within the PE and NPE cell layers are inadequate to maintain constancy of ionic composition throughout the epithelium under certain conditions. Although many hormones, drugs and signaling cascades are known to have effects, a persuasive model of the regulation of aqueous humor formation has not yet been developed. cAMP likely plays a central role, potentially both enhancing and reducing secretion by actions at both surfaces of the ciliary epithelium. Among other hormone receptors, A(3) adenosine receptors likely alter intraocular pressure by regulating NPE-cell Cl(-) channel activity. Recently, functional evidence for the regional variation in ciliary epithelial secretion has been demonstrated; the physiologic and pathophysiologic implications of this regional variation remain to be addressed.

Aqueous humour (AH) is an important intraocular fluid responsible for the supply of nutrients to and removal of metabolic wastes from the avascular tissues of the eye. It is also indispensable for the maintenance of the optical properties of the eye. The fluid dynamics of AH are frequently associated with the potentially blinding disease called glaucoma. Pharmacological treatment of glaucoma generally aims to lower the intraocular pressure by reducing AH formation. However, the mechanism underlying the formation of AH is still not well understood. Understanding the mechanism of AH formation and its regulation is paramount to develop rational and target specific drugs for the treatment of glaucoma. It is now generally believed that AH is formed mostly by active transport of ions and solutes across the ciliary epithelium. Many studies have been carried out in the past half a century to understand these transport processes. In the past several years, new information has emerged and a comprehensive review of these new developments is necessary. This review covers the ion transports in the ciliary epithelium, including the possible roles of sodium, chloride and bicarbonate ions as the driving forces. It also examines the current ionic models for AH formation and its regulation from a cellular transport perspective.

Although glaucoma treatments alter aqueous humor (AH) dynamics to lower intraocular pressure, the regulatory mechanisms of AH circulation and their contributions to the pathogenesis of ocular hypertension and glaucoma remain unclear. We hypothesized that gadolinium-enhanced magnetic resonance imaging (Gd-MRI) can visualize and assess AH dynamics upon sustained intraocular pressure elevation and pharmacologic interventions.Gadolinium contrast agent was systemically administered to adult rats to mimic soluble AH components entering the anterior chamber (AC) via blood-aqueous barrier. Dynamic Gd-MRI was applied to examine the signal enhancement in AC and vitreous body upon microbead-induced ocular hypertension and unilateral topical applications of latanoprost, timolol maleate, and brimonidine tartrate to healthy eyes.Gadolinium signal time courses in microbead-induced hypertensive eyes possessed faster initial gadolinium uptake and higher peak signals in AC than control eyes, reflective of reduced gadolinium clearance upon microbead occlusion. Opposite trends were observed in latanoprost- and timolol-treated eyes, indicative of their respective drug actions on increased uveoscleral outflow and reduced AH production. The slowest initial gadolinium uptake but strongest peak signals were found in AC of both brimonidine-treated and untreated fellow eyes. These findings drew attention to the systemic effects of topical hypotensive drug treatment. Gadolinium leaked into the vitreous of microbead-induced hypertensive eyes and brimonidine-treated and untreated fellow eyes, suggestive of a compromise of aqueous-vitreous or blood-ocular barrier integrity.Gadolinium-enhanced MRI allows spatiotemporal and quantitative evaluation of altered AH dynamics and ocular tissue permeability for better understanding the physiological mechanisms of ocular hypertension and the efficacy of antiglaucoma drug treatments.

The mouse is a useful laboratory animal model for studying glaucoma and human aqueous humor dynamics, thereby facilitating evaluation of drugs1–3 and genetic manipulations.4,5 Lowering intraocular pressure (IOP) is the only clinical intervention documented to delay the onset and slow the rate of progression of irreversible blindness in glaucoma,6–8 so that accurate and precise measurement of IOP in the small mouse eye is central to studying glaucoma mechanisms in mice. IOP is fundamentally dependent on arterial delivery of solute and water to and venous drainage from the eye.9 When the perfusion pressure (mean arterial pressure minus IOP) falls below a critical level, the rate of aqueous humor formation becomes dependent on ciliary blood flow,10,11 so relating cardiac to aqueous dynamics is also highly pertinent. Several approaches have been applied to measure the IOP of the small mouse eye. The most conventional method is to estimate IOP manometrically by cannulating the eye with a microneedle 45 to 50 μm in diameter,12,13 but leakage around the relatively large-bore microneedle can occur12 and probably leads to underestimates and variability of the measured values.3 The servo-null micropipette system (SNMS) is an electrophysiologic approach that has been fully validated for measuring mouse IOP,3 but it is also invasive and requires expensive equipment and specialized training for performing the measurements. Applanation tonometry has also been adapted to the mouse,14 but the technique requires a specially designed prism and has been criticized because of the subjective endpoint of measurement.15 Recently, an induction-impact tonometer has been adapted.15 This device is sensitive to changes in IOP at low-normal ranges, but is relatively insensitive to changes in the high range and shows significant variance. As a result, the readout changes very little over the range of 25 to 35 mm Hg,15 limiting its usefulness in the study of glaucomatous mice. Most recently, a handheld tonometer (Tonopen; Mentor, Norwell, MA) has been applied to the mouse for measuring IOP and validated through comparisons with the SNMS and detection of the ocular hypotensive effect of brimonidine.16 However, as pointed out by the investigators, the time resolution is limited, precluding measurement of pulsatility or rapid responses of IOP to drugs. A further consideration is the substantial variance in single measurements of a single eye.16,17 In the current study, we assessed whether an adaptation of pneumotonometry might be useful in measuring IOP in mice.

PURPOSE To investigate the potential significance of cAMP in the regulation of Cl(-) transport across the bovine ciliary body/epithelium (CBE). METHODS Fresh native bovine CBE preparation was mounted in a modified Ussing chamber. The effects of cAMP-stimulating agents on short-circuit current (I(sc)) and net (36)Cl(-) secretion were determined. RESULTS Addition of cAMP-stimulating agents inhibited net Cl(-) secretion. Forskolin, when added bilaterally, reduced Cl(-) secretion by 60%. Similarly, bilateral isoproterenol or vasoactive intestinal peptide inhibited Cl(-) transport by 15% and 37%, respectively, suggesting a cAMP-sensitive Cl(-) transport across the ciliary epithelium. This notion was supported by the exogenous application of 8-bromo-cAMP (8-Br-cAMP) or 3-isobutyl-1-methylxanthine (IBMX), which reduced the net Cl(-) secretion by 49% and 85%, respectively. In unstimulated preparations, addition of 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) to the blood side had no effects on I(sc) and net Cl(-) transport, indicating that Cl(-) reabsorption was negligible under baseline conditions. Also, pretreatment with NPPB from the blood side did not prevent forskolin-induced I(sc) inhibition, suggesting that the inhibition of Cl(-) transport did not result from the facilitation of Cl(-) reabsorption. However, pretreatment with heptanol from both sides completely blocked the forskolin-induced I(sc) inhibition, suggesting that cAMP may reduce Cl(-) transport by uncoupling the intercellular gap junctions. CONCLUSIONS The results suggest that cAMP plays a crucial role in modulating Cl(-) secretion across the ciliary epithelium. The effect is possibly mediated, at least in part, by the regulation of the permeability of gap junctions between pigmented and nonpigmented ciliary epithelial cells.