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Age-related macular degeneration (AMD) is a degenerative eye disease leading to central vision loss and is characterized by dysregulated autophagy of the retinal pigment epithelium (RPE) layer. Recent studies have suggested that rho-associated protein kinase (ROCK) inhibitors may enhance autophagy in neurodegenerative diseases and promote the survival of RPE cells. This study investigated the effect of ROCK inhibitors on autophagy gene expression and autophagic vacuole formation in a human RPE (ARPE-19) cell line. The highly selective and potent ROCK inhibitor Y-39983 enhanced the expression of autophagy genes in ARPE-19 cells and increased autophagic vacuole formation. A proteomic analysis using mass spectrometry was performed to further characterize the effects of ROCK inhibition at the protein level. Y-39983 downregulated thrombospondin-1 (THBS1), and suppression of THBS1 in ARPE-19 cells resulted in an increase in autophagic vacuole formation. Our data showed that ROCK inhibitor-induced autophagy was mediated by THBS1 downregulation. We identified ROCK and THBS1 as potential novel therapeutic targets in AMD. [ABSTRACT FROM AUTHOR]

PurposeIt has been proposed that the peripheral retina, responding to local optical defocus, contributes to myopia and associated altered eye growth in humans. To test this hypothesis, we measured the changes in central (on-axis) and peripheral ocular dimensions in guinea pigs wearing a concentric bifocal spectacle lens design with power restricted to the periphery.MethodsFive groups of guinea pigs (n = 83) wore either a unifocal (UF) spectacle lens (-4, 0, or +4 Diopters [D]), or a peripheral defocus (PF) spectacle lens that had a plano center (diameter of 5 mm) with either -4 or +4 D in the surround (-4/0 or +4/0 D). The overall optical diameter of all lenses was 12 mm. Lenses were worn over one eye from 8 to 18 days of age for negative and plano lenses, or from 8 to 22 days of age for positive lenses. Refractive error was measured centrally and 30° off-axis in the temporal and nasal retina. The shape of the eye was analyzed from images of sectioned eyes.ResultsLenses of -4 D UF induced myopia, reflecting enhanced ocular elongation, which was centered on the optic nerve head and included the surrounding peripapillary zone (PPZ, 18° in diameter). Some ocular expansion, including within the PPZ, also was recorded with -4/0 and +4/0 D PF lenses while the +4 D UF lens inhibited rather than enhanced elongation, centrally and peripherally.ConclusionsPeripheral defocus-induced ocular expansion encompasses the PPZ, irrespective of the sign of the inducing defocus. Understanding the underlying mechanism potentially has important implications for designing multifocal lenses for controlling myopia in humans and also potentially for understanding the link between myopia and glaucoma.

Neurodegenerative diseases characterized by aberrant accumulation of undigested cellular components represent unmet medical conditions for which the identification of actionable targets is urgently needed. Here we identify a pharmacologically actionable pathway that controls cellular clearance via Akt modulation of transcription factor EB (TFEB), a master regulator of lysosomal pathways. We show that Akt phosphorylates TFEB at Ser467 and represses TFEB nuclear translocation independently of mechanistic target of rapamycin complex 1 (mTORC1), a known TFEB inhibitor. The autophagy enhancer trehalose activates TFEB by diminishing Akt activity. Administration of trehalose to a mouse model of Batten disease, a prototypical neurodegenerative disease presenting with intralysosomal storage, enhances clearance of proteolipid aggregates, reduces neuropathology and prolongs survival of diseased mice. Pharmacological inhibition of Akt promotes cellular clearance in cells from patients with a variety of lysosomal diseases, thus suggesting broad applicability of this approach. These findings open new perspectives for the clinical translation of TFEB-mediated enhancement of cellular clearance in neurodegenerative storage diseases.

Purpose: Uncorrected refractive error is the leading cause of vision impairment globally; however, little attention has been given to equity and access to services. This study aimed to identify and prioritise: (1) strategies to address inequity of access to refractive error services and (2) population groups to target with these strategies in five sub‐regions within the Western Pacific. Methods: We invited eye care professionals to complete a two‐round online prioritisation process. In round 1, panellists nominated population groups least able to access refractive error services, and strategies to improve access. Responses were summarised and presented in round 2, where panellists ranked the groups (by extent of difficulty and size) and strategies (in terms of reach, acceptability, sustainability, feasibility and equity). Groups and strategies were scored according to their rank within each sub‐region. Results: Seventy five people from 17 countries completed both rounds (55% women). Regional differences were evident. Indigenous peoples were a priority group for improving access in Australasia and Southeast Asia, while East Asia identified refugees and Oceania identified rural/remote people. Across the five sub‐regions, reducing out‐of‐pocket costs was a commonly prioritised strategy for refraction and spectacles. Australasia prioritised improving cultural safety, East Asia prioritised strengthening school eye health programmes and Oceania and Southeast Asia prioritised outreach to rural areas. Conclusion: These results provide policy‐makers, researchers and funders with a starting point for context‐specific actions to improve access to refractive error services, particularly among underserved population groups who may be left behind in existing private sector‐dominated models of care. [ABSTRACT FROM AUTHOR]

PurposeEye growth compensates in opposite directions to single vision (SV) negative and positive lenses. We evaluated the response of the guinea pig eye to Fresnel-type lenses incorporating two different powers.MethodsA total of 114 guinea pigs (10 groups with 9-14 in each) wore a lens over one eye and interocular differences in refractive error and ocular dimensions were measured in each of three experiments. First, the effects of three Fresnel designs with various diopter (D) combinations (-5D/0D; +5D/0D or -5D/+5D dual power) were compared to three SV lenses (-5D, +5D, or 0D). Second, the ratio of -5D and +5D power in a Fresnel lens was varied (50:50 compared with 60:40). Third, myopia was induced by 4 days of exposure to a SV -5D lens, which was then exchanged for a Fresnel lens (-5D/+5D) or one of two SV lenses (+5D or -5D) and ocular parameters tracked for a further 3 weeks.ResultsDual power lenses induced an intermediate response between that to the two constituent powers (lenses +5D, +5D/0D, 0D, -5D/+5D, -5D/0D and -5D induced +2.1 D, +0.7 D, +0.1 D, -0.3 D, -1.6 D and -5.1 D in mean intraocular differences in refractive error, respectively), and changing the ratio of powers induced responses equal to their weighted average. In already myopic animals, continued treatment with SV negative lenses increased their myopia (from -3.3 D to -4.2 D), while switching to SV positive lenses or -5D/+5D Fresnel lenses reduced their myopia (by 2.9 D and 2.3 D, respectively).ConclusionsThe mammalian eye integrates competing defocus to guide its refractive development and eye growth. Fresnel lenses, incorporating positive or plano power with negative power, can slow ocular growth, suggesting that such designs may control myopia progression in humans.

Background: Myopia, characterized by excessive axial elongation of the eyeball, increases risks of having sight-threatening diseases and impose a financial burden to healthcare system. Although myopic control interventions showed their effectiveness in slowing progression, the efficacy varies between individuals and does not completely halt progression. The study aims to investigate the efficacy of combining 0.01% atropine administered twice daily with optical defocus for myopia control in schoolchildren. Methods and design: This is a prospective, parallel-group, single-blinded, randomized, active-control trial (ClinicalTrials.gov identifier: NCT06358755). Myopic schoolchildren with no previous myopic control interventions aged between 7 to 12 years will be recruited. They will be randomly allocated into two groups (n = 56 per group) after baseline measurement. Both groups will receive 0.01% atropine twice per day for 18 months (one drop in the morning and the other drop at night before bedtime). Defocus incorporated multiple segments (DIMS) spectacle lenses will be prescribed in atropine plus optical defocus (ATD) treatment group while single vision spectacle lenses will be given in atropine only (AT) group. Cycloplegic refraction and axial lengths will be monitored every 6 months over 18-month study period. The primary outcomes are changes in cycloplegic refraction and axial lengths relative to the baseline over the study period. Discussion: The result will examine the combination effect of low dose atropine and myopic defocus on myopia control in a randomized controlled study. The findings will also explore the potential benefits of applying 0.01% atropine twice per day on myopic control and its potential side effects. [ABSTRACT FROM AUTHOR]

Purpose: To investigate changes in relative peripheral refraction (RPR) associated with myopia progression in children who wore single‐vision (SV) lenses for 2 years and switched to Defocus Incorporated Multiple Segments (DIMS) lenses in the third year versus children who wore DIMS lenses for 3 years. Methods: In the first 2 years, children were allocated randomly to wear either DIMS or SV lenses. In the third year, children in the DIMS group continued to wear these lenses, while those in the SV group were switched to DIMS lenses (Control‐to‐DIMS group). Central and peripheral refraction and axial length were monitored every 6 months. Results: Over 3 years, the DIMS group (n = 65) showed good myopia control and maintained a relatively constant and symmetrical RPR profile without significant changes. In the first 2 years, children who wore SV lenses (n = 55) showed asymmetrical RPR changes, with significant increases in hyperopic RPR at 20° nasal (N) (mean difference: 0.88 ± 1.06 D, p < 0.0001) and 30N (mean difference: 1.07 ± 1.09 D, p < 0.0001). The Control‐to‐DIMS group showed significant myopia retardation after wearing DIMS lenses in the third year. When compared with the RPR changes in the first 2 years, significant reductions in hyperopic RPR were observed at 20N (mean difference: −1.14 ± 1.93 D, p < 0.0001) and 30N (mean difference: −1.07 ± 1.17 D, p < 0.0001) in the third year. However, no significant difference between the RPR changes found in the nasal retina and temporal retina (p > 0.05) was noted in the third year. Conclusion: Symmetrical changes in RPR were found in children switching from SV to DIMS lenses, and a symmetrical pattern of RPR was noted in children who wore DIMS for 3 years. Myopia control using myopic defocus in the mid‐periphery influenced the RPR changes and retarded myopia progression by altering the eye's growth pattern. [ABSTRACT FROM AUTHOR]

Eye size is a key parameter of visual function, but the precise mechanisms of eye size control remain poorly understood. Here, we discovered that the lipogenic transcription factor sterol regulatory element-binding protein 2 (SREBP2) has an unanticipated function in the retinal pigment epithelium (RPE) to promote eye size in postnatal mice. SREBP2 transcriptionally represses low density lipoprotein receptor-related protein 2 (Lrp2), which has been shown to restrict eye overgrowth. Bone morphogenetic protein 2 (BMP2) is the downstream effector of Srebp2 and Lrp2, and Bmp2 is suppressed by SREBP2 transcriptionally but activated by Lrp2. During postnatal development, SREBP2 protein expression in the RPE decreases whereas that of Lrp2 and Bmp2 increases as the eye growth rate reduces. Bmp2 is the key determinant of eye size such that its level in mouse RPE inversely correlates with eye size. Notably, RPE-specific Bmp2 overexpression by adeno-associated virus effectively prevents the phenotypes caused by Lrp2 knock out. Together, our study shows that rapid postnatal eye size increase is governed by an RPE-derived signaling pathway, which consists of both positive and negative regulators of eye growth. [ABSTRACT FROM AUTHOR]

Aim To determine if 'Defocus Incorporated Multiple Segments' (DIMS) spectacle lenses slow childhood myopia progression. Methods A 2-year double-masked randomised controlled trial was carried out in 183 Chinese children aged 8-13 years, with myopia between -1.00 and -5.00 D and astigmatism =1.50 D. Children were randomly assigned to wear DIMS (n=93) or single vision (SV) spectacle lenses (n=90). DIMS lens incorporated multiple segments with myopic defocus of +3.50 D. Refractive error (cycloplegic autorefraction) and axial length were measured at 6month intervals. Results 160 children completed the study, n=79 in the DIMS group and n=81 in the SV group. Average (SE) myopic progressions over 2 years were -0.41±0.06 D in the DIMS group and -0.85±0.08 D in the SV group. Mean (SE) axial elongation was 0.21±0.02 mm and 0.55±0.02 mm in the DIMS and SV groups, respectively. Myopia progressed 52% more slowly for children in the DIMS group compared with those in the SV group (mean difference -0.44±0.09 D, 95% CI -0.73 to -0.37, p<0.0001). Likewise, children in the DIMS group had less axial elongation by 62% than those in the SV group (mean difference 0.34±0.04 mm, 95% CI 0.22 to 0.37, p<0.0001). 21.5% children who wore DIMS lenses had no myopia progression over 2 years, but only 7.4% for those who wore SV lenses. Conclusions Daily wear of the DIMS lens significantly retarded myopia progression and axial elongation in myopic children. Our results demonstrated simultaneous clear vision with constant myopic defocus can slow myopia progression. [ABSTRACT FROM AUTHOR]