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Reduced levels of retinal dopamine, a key regulator of eye development, are associated with experimental myopia in various species, but are not seen in the myopic eyes of C57BL/6 mice, which are deficient in melatonin, a neurohormone having extensive interactions with dopamine. Here, we examined the relationship between form-deprivation myopia (FDM) and retinal dopamine levels in melatonin-proficient CBA/CaJ mice. We found that these mice exhibited a myopic refractive shift in form-deprived eyes, which was accompanied by altered retinal dopamine levels. When melatonin receptors were pharmacologically blocked, FDM could still be induced, but its magnitude was reduced, and retinal dopamine levels were no longer altered in FDM animals, indicating that melatonin-related changes in retinal dopamine levels contribute to FDM. Thus, FDM is mediated by both dopamine level-independent and melatonin-related dopamine level-dependent mechanisms in CBA/CaJ mice. The previously reported unaltered retinal dopamine levels in myopic C57BL/6 mice may be attributed to melatonin deficiency. [ABSTRACT FROM AUTHOR]

Myopia is the most common cause of refractive error worldwide. High myopia is a severe type of myopia, which usually accompanies pathological changes in the fundus. To identify high myopia susceptibility genes, DNA-pooling based genome-wide association analysis was used to search for a correlation between single nucleotide polymorphisms and high myopia in a Han Chinese cohort (cases vs. controls in discovery stage: 507 vs. 294; replication stage 1: 991 vs. 1,025; replication stage 2: 1,021 vs. 52,708). Three variants (rs10889602T/G, rs2193015T/C, rs9676191A/C) were identified as being significantly associated with high myopia in the discovery, and replication stage. rs10889602T/G is located at the third intron of phosphodiesterase 4B (PDE4B), whose functional assays were performed by comparing the effects of rs10889602T/T deletion of this risk allele on PDE4B and COL1A1 gene and protein expression levels in the rs10889602T/Tdel/del, rs10889602T/Tdel/wt, and normal control A549 cell lines. The declines in the PDE4B and COL1A1 gene expression levels were larger in the rs10889602T/T deleted A549 cells than in the normal control A549 cells (one-way ANOVA, p < 0.001). The knockdown of PDE4B by siRNA in human scleral fibroblasts led to downregulation of COL1A1. This correspondence between the declines in rs10889602 of the PDE4B gene, PDE4B knockdown, and COL1A1 protein expression levels suggest that PDE4B may be a novel high myopia susceptibility gene, which regulates myopia progression through controlling scleral collagen I expression levels. More studies are needed to determine if there is a correlation between PDE4B and high myopia in other larger sample sized cohorts. [ABSTRACT FROM AUTHOR]

Myopia is a substantial public health problem worldwide. In the myopic retina, distant images are focused in front of the photoreceptors. The cells and mechanisms for retinal signaling that account either for emmetropization (i.e., normal refraction) or for refractive errors have remained elusive. Gap junctions play a key component in enhancement of signal transmission in visual pathways. AII amacrine cells (ACs), coupled by connexin36, segregate signals into ON and OFF pathways. Coupling between AII ACs is actively modulated through phosphorylation at serine 293 via dopamine in the mouse retina. In this study, form deprivation mouse myopia models were used to evaluate the expression patterns of connexin36-positive plaques (structural assay) and the state of connexin36 phosphorylation (functional assay) in AII ACs, which was green fluorescent protein-expressing in the Fam81a mouse line. Single-cell RNA sequencing showed dopaminergic synapse and gap junction pathways of AII ACs were downregulated in the myopic retina, although Gjd2 mRNA expression remained the same. Compared with the normal refractive eye, phosphorylation of connexin36 was increased in the myopic retina, but expression of connexin36 remained unchanged. This increased phosphorylation of Cx36 could indicate increased functional gap junction coupling of AII ACs in the myopic retina, a possible adaptation to adjust to the altered noisy signaling status. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the relative proportion of conjunctival MUC5AC+ and MUC5AC− goblet cells in a post-LASIK population and their association with dry eye indicators and corneal nerve morphology using a MUC5AC+ Goblet Cell Index.Methods: Twenty subjects who had undergone LASIK > 12 months previously and 20 age-matched controls were recruited. Dry eye symptoms, tear breakup time, osmolarity, meniscus area and corneal nerve morphology were examined. Conjunctival impression cytology samples were collected from inferior-temporal bulbar conjunctiva using Millicell® inserts. Total goblet cell density was determined from positive cytokeratin-7 (CK7) immunolabelling; MUC5AC+ goblet cell density was determined from both CK7+- and MUC5AC+-immunolabelled cells. The ratio of MUC5AC+ to total density was defined as the “MUC5AC+ Goblet Cell Index”. Differences in variables between groups and the associations between goblet cell variables and clinical assessments were examined.Results: No significant differences in the total and MUC5AC+ goblet cell density and tear film parameters were found between groups, although greater ocular discomfort was reported in the post-LASIK group (P = 0.02). A higher MUC5AC+ Index was associated with worse/greater dry eye symptoms (ρ = 0.55, P = 0.01) and higher nerve tortuosity (ρ = 0.57, P = 0.01) in the post-LASIK group; lower nerve density and thickness was found in controls (ρ > −0.45, P < 0.05), but not associated with tear film parameters.Conclusions: The MUC5AC+ Goblet Cell Index provides an indicator of mucin secretion for assessing the goblet cell function in dry eye. In the post-LASIK participants, we found an increased MUC5AC+ Index associated with worse dry eye symptoms and adverse changes in corneal nerve morphology. [ABSTRACT FROM AUTHOR]

Abstract: Retinal arachidonic acid (ARA) levels in form‐deprived eyes decline in guinea pigs. As prostaglandin F2α (PGF2α) is an ARA metabolite and endogenous agonist of prostaglandin F receptor (FP), we have been suggested that down‐regulation of PGF2α‐FP receptor signalling pathway contributes to myopia onset. To test this hypothesis, this study determines whether: (i) retinal PGF2α levels decline during the development of form deprivation myopia (FDM) in guinea pigs; (ii) FP receptor agonism and antagonism alter emmetropization and myopia development. Pigmented guinea pigs were randomly assigned to normal vision and form‐deprived groups. Ultraperformance liquid chromatography coupled with a mass spectrometer (UPLC‐MS) measured retinal PGF2α levels 2 weeks after form deprivation (FD). The selective FP agonist, latanoprost acid (LAT) and its corresponding antagonist, AL8810, were peribulbarly injected into each group. An eccentric infrared photorefractor (EIR) monitored refraction. A‐scan ultrasonography measured axial elongation (AL) and vitreous chamber depth (VCD). Tonometry measured the intraocular pressure (IOP). Retinal PGF2α levels declined in form‐deprived eyes compared to those in normal eyes. Neither LAT nor AL8810 affected IOP with or without FD. On the other hand, after 4 weeks of daily 0.5 μg AL8810 treatment, a myopia of −1.99 ± 0.34 dioptre (D) developed, but LAT had no effect on emmetropization in a normal visual environment. Nevertheless, daily 30 μg LAT treatment for 4 weeks inhibited FDM development by 41% (vehicle control: −8.39 ± 0.45 D; LAT: −4.95 ± 0.39 D; two‐way anova with repeated measures, p < 0.05). Down‐regulation of PGF2α‐FP receptor signalling pathway may contribute to myopia onset as retinal PGF2α declined in myopic eyes and antagonism of FP receptor by AL8810 induced a myopic shift in normal vision environment. Meanwhile, up‐regulation of this pathway by LAT inhibited FDM development. However, the mechanism underlying LAT‐induced FDM inhibition needs further clarification. This uncertainty exists because its inhibition of FDM suggests that LAT strengthens the scleral framework which reduces axial elongation. On the other hand, its IOP‐lowering effect is attributed to thinning and weakening the scleral framework in glaucoma treatment. [ABSTRACT FROM AUTHOR]

Leber's hereditary optic neuropathy (LHON) is one of the most common mitochondrial disorders. We report here the clinical, genetic and molecular analysis of mitochondrial DNA (mtDNA) in eight Han Chinese families carrying the known mitochondrial 11778G > A(MT-ND4) mutation. Thirty-seven (26 males/11 females) of 77 matrilineal relatives in these families exhibited the variable severity and age-at-onset of optic neuropathy. The penetrances were from 25% to 75%, with the average of 42%, and the age-at-onset for visual impairment varied from 10 to 25 years, with the average of 17 in these Chinese pedigrees. Molecular analysis of their mtDNA identified distinct sets of variants belonging to the Eastern Asian haplogroupD4j. Except the known m.11778G > A mutation, the m.11696G > A(MT-ND4) mutation caused the substitution of an isoleucine for valineat amino acid position 313, located in a predicted transmembrane region of ND4. And, it is reported that the m.11696G > A mutation was associated with LHON, and appeared to contribute to higher penetrance in these nine Chinese families than other Chinese families carrying only the m.11778G > A mutation. Therefore, the mitochondrial haplogroup D4j specific m.11696G > A mutation may act in synergy with the primary LHON-associated m.11778G > A mutation, thereby increasing the penetrance and expressivity of visual loss in these Chinese families. [ABSTRACT FROM PUBLISHER]

Purpose: The most likely etiology of post-LASIK dry eye is corneal nerve damage; however, no direct relationship between post-LASIK dry eye symptoms and nerve damage has been established, and limited information is available about the relationship between dry eye signs and corneal reinnervation after LASIK. Tear neuropeptides (SP and CGRP) are important in the maintenance of corneal nerve health, but the impact of LASIK has not yet been studied. This study evaluated changes in nerve morphology, tear neuropeptide, and dry eye, so as to establish the relationship between reinnervation and dry eye and to assess the role of tear neuropeptides in reinnervation post-LASIK. Methods: Twenty non-dry eye volunteers who had undergone bilateral myopic-LASIK completed this study. Corneal nerve morphology (density, width, interconnections, and tortuosity), SP and CGRP concentration, and dry eye were monitored over time prior to, 1 day, 1 week, 1, 3, and 6 months post-LASIK. Results: Dry eye symptoms and tear function, except for osmolarity ( P = 0.003), remained unchanged post-LASIK. Corneal nerve morphology decreased immediately, and did not return to preoperative levels by 6 months post-LASIK ( P < 0.001). Increased tear SP concentration was observed 3 months post-LASIK ( P < 0.001). Associations between reinnervation as measured by increased density and lower tear SP ( P = 0.03), and between increased density and decreased dry eye symptoms ( P = 0.01) were found post-LASIK. Conclusion: An inverse relationship between reinnervation post-LASIK and dry eye symptoms was found, confirming that post-LASIK dry eye is a neuropathic disease. This study is the first to demonstrate an association between tear SP and post-LASIK reinnervation, suggesting that strategies for manipulating neuropeptide concentration to improve reinnervation may improve ocular comfort post-LASIK. [ABSTRACT FROM AUTHOR]

Myopia incidence in China is rapidly becoming a very serious sight compromising problem in a large segment of the general population. Therefore, delineating the underlying mechanisms leading to myopia will markedly lessen the likelihood of other sight compromising complications. In this regard, there is some evidence that patients afflicted with familial adenomatous polyposis (FAP), havean adenomatous polyposis coli (APC) mutation and a higher incidence of myopia. To clarify this possible association, we determined whether the changes in pertinent biometric and biochemical parameters underlying postnatal refractive error development in APCMin mice are relevant for gaining insight into the pathogenesis of this disease in humans. The refraction and biometrics in APCMin mice and age-matched wild-type (WT) littermates between postnatal days P28 and P84 were examined with eccentric infrared photorefraction (EIR) and customized optical coherence tomography (OCT). Compared with WT littermates, the APCMin mutated mice developed myopia (average -4.64 D) on P84 which was associated with increased vitreous chamber depth (VCD). Furthermore, retinal and scleral changes appear in these mice along with: 1) axial length shortening; 2) increased retinal cell proliferation; 3) and decreased tyrosine hydroxylase (TH) expression, the rate-limiting enzyme of DA synthesis. Scleral collagen fibril diameters became heterogeneous and irregularly organized in the APCMin mice. Western blot analysis showed that scleral alpha-1 type I collagen (col1α1) expression also decreased whereas MMP2 and MMP9 mRNA expression was invariant. These results indicate that defective APC gene function promotes refractive error development. By characterizing in APCMin mice ocular developmental changes, this approach provides novel insight into underlying pathophysiological mechanisms contributing to human myopia development. [ABSTRACT FROM AUTHOR]

Purpose This study investigated whether pilocarpine and cyclopentolate induce changes in ocular biometry of guinea pigs, in order to understand if guinea pigs have a similar response to these two agents as humans do. Methods Under general anaesthesia, refraction, axial components and surface curvature in various optical interfaces of the eye were measured in 10 guinea pigs (age of 2 weeks) at baseline (0 min) and different time points (5, 10, 20, 30, 60, 90 min) after topical administration of pilocarpine or cyclopentolate. The interval between the two drug treatments for the same animals was at least 24 h. Results Eyes treated with pilocarpine developed approximately 6D myopia ( p < 0.001 from 0 to 90 min) with a decrease in anterior lens radius of curvature ( ALRC) ( p < 0.001 from 0 to 90 min, repeated measures anova). This myopic shift was moderately correlated to the decreased ALRC ( r2 = 0.48, p < 0.001). Furthermore, a small but significant increase in the VCD ( p < 0.001 from 0 to 30 min, repeated measures anova) with an unchanged AL ( p = 0.85 from 0 to 90 min, repeated measures anova) after the drug treatment suggested a transient and mild forward movement of the lens. Cyclopentolate dilated the pupil in all eyes ( p < 0.001 from 0 to 90 min, repeated measures anova) but did not change other ocular parameters. Conclusions The muscarinic agonist, pilocarpine induced a myopic shift mainly due to a decrease in ALRC, suggesting that guinea pigs have an accommodative mechanism similar to that in humans. The minimal changes produced by cyclopentolate could be due to the use of general anaesthesia, which may have reduced the susceptibility of the eye to topical cyclopentolate in the induction of cycloplegia. [ABSTRACT FROM AUTHOR]

The development of myopia is associated with decreased ocular scleral collagen synthesis in humans and animal models. Collagen synthesis is, in part, under the influence of cyclic adenosine monophosphate (cAMP). We investigated the associations between cAMP, myopia development in guinea pigs, and collagen synthesis by human scleral fibroblasts (HSFs). Form-deprived myopia (FDM) was induced by unilateral masking of guinea pig eyes. Scleral cAMP levels increased selectively in the FDM eyes and returned to normal levels after unmasking and recovery. Unilateral subconjunctival treatment with the adenylyl cyclase (AC) activator forskolin resulted in a myopic shift accompanied by reduced collagen mRNA levels, but it did not affect retinal electroretinograms. The AC inhibitor SQ22536 attenuated the progression of FDM. Moreover, forskolin inhibited collagen mRNA levels and collagen secretion by HSFs. The inhibition was reversed by SQ22536. These results demonstrate a critical role of cAMP in control of myopia development. Selective regulation of cAMP to control scleral collagen synthesis may be a novel therapeutic strategy for preventing and treating myopia. [ABSTRACT FROM AUTHOR]

Myopia is a refractive error of the eye that is prevalent worldwide. The most extreme form, high myopia, is usually associated with other ocular disorders such as retinal detachment, macular degeneration, cataract, and glaucoma, and is one of leading causes of blindness. The etiology is complex and has not been fully elucidated. In this study, we identified a novel missense variant of the CCDC111 gene (NM_152683.2: c.265T > G; p.Y89D) in a high myopia family by exome sequencing. The variant was identified in 4 patients from an additional 270 sporadic high myopia patients, but not found in 270 controls. The amino acid is highly conserved across species, and variants giving rise to amino acid substitutions are predicted to be functionally damaging. The CCDC111 gene was ubiquitously expressed in primary cell cultures from human eye tissue, including corneal epithelial cells, choroidal melanoma cells, scleral fibroblasts, retinal epithelial cells, retinal Müller cells, and lens capsule epithelial cells. In summary, our results suggested that the CCDC111 may be a susceptibility gene for high myopia. [ABSTRACT FROM AUTHOR]

Herein, we report on the synthesis of film-forming poly(styrene- co-butyl acrylate- co-acrylic acid)/SiO [P(St-BA-AA)/SiO] nanocomposites by in situ formation of SiO nanoparticles from TEOS via sol-gel process in the presence of poly(acrylic acid) (PAA)-functionalized poly(styrene- co-butyl acrylate) [P(St-BA)] particles fabricated by soap-free emulsion polymerization. The formed silica particles could be absorbed by polyacrylate chains on the surface of PAA-functionalized P(St-BA) particles; thus, raspberry-like polymer/silica nanocomposites would be obtained. Transmission electron microscopy, Fourier transform infrared spectroscopy, attenuated total reflectance infrared spectrum, ultraviolet-visible transmittance spectra, and thermogravimetric analysis were used to characterize the resulting composites. The results showed that the hybrid polymer/silica had a raspberry-like structure with silica nanoparticles anchored on the surface of polymer microspheres. The thermal, fire retardant, and mechanical properties and water resistance of the film were improved by incorporating silica nanoparticles, while the optical transmittance was seldom affected due to nanosized silica particles uniformly dispersed in the film. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Purpose: Whether there is an interaction between eyes of individual subjects in refractive development is an important issue to guide experimental designs and help understand mechanisms involved in development of refractive errors. This study investigated whether spontaneous high myopia in one eye will affect refractive development of the fellow eye treated with form deprivation. Methods: Thirty-four guinea pigs were divided into four groups: MD (monocularly form-deprived animals with a pre-treatment anisometropia ≤≤ 2D, n == 8), anisometropic MD (monocular form deprivation on a relatively hyperopic eye in animals with a pre-treatment anisometropia ≥≥ 10D, n == 9), normal control (non-form deprivation in animals with a pre-treatment anisometropia ≤≤ 2D, n == 8), and anisometropic control (non-form deprivation in animals with a pre-treatment anisometropia ≥≥ 10D, n == 9). All eyes in different groups underwent biometric measurements on days 0, 12, 24, and 36 of the experiment. Results: High myopia in one eye reduced form deprivation myopia in the fellow treated eye. The change in refraction from 0 to 36 days in the deprived eyes was -3.07D for the MD group, but -1.22D for the anisometropic MD group (-3.07D vs. -1.22D: p == 0.009, independent sample t-test). The amount of vitreous chamber lengthening over the same period in the deprived eyes was 0.19 mm for the MD group, but 0.12 mm for the anisometropic MD group (0.19 mm vs. 0.12 mm: p == 0.038, independent sample t-test). Myopic development in the anisometropic animals is mainly inhibited within the first 12 days compared to normal MD animals. Conclusions: These results indicate that an interaction in refractive development may exist temporarily between two eyes of a highly anisometropic animal if the visual environment has been changed. [ABSTRACT FROM AUTHOR]

Refolding of proteins at high concentrations often results in non-productive aggregation. This study, through a unique combination of spectroscopic and chromatographic analyzes, provides biomolecular evidence to demonstrate the ability of Eudragit S-100, a pH-responsive polymer, to enhance refolding of denatured-reduced lysozyme at high concentrations. The addition of Eudragit in the refolding buffer significantly increases lysozyme refolding yield to 75%, when dilution refolding was conducted at 1 mg/mL lysozyme. This study shows evidence of an electrostatic interaction between oppositely charged lysozyme and the Eudragit polymer during refolding. This ionic complexing of Eudragit and lysozyme appears to shield exposed hydrophobic residues of the lysozyme refolding intermediates, thus minimizing hydrophobic-driven aggregation of the molecules. Importantly, results from this study show that the Eudragit-lysozyme bioconjugation does not compromise refolded protein structure, and that the polymer can be readily dissociated from the protein by ion exchange chromatography. The strategy was also applied to refolding of TGF-β1 and KGF-2. © 2009 American Institute of Chemical Engineers Biotechnol. Prog. 2009 [ABSTRACT FROM AUTHOR]

Purpose: This study used two-dimensional gel electrophoresis (2-DE) to analyze protein profiles for normal human scleral fibroblasts in order to provide a baseline for future study of proteomics of the sclera in experimental conditions. In addition, differences in the presence and amount of proteins from fibroblasts isolated from the anterior or posterior sclera were analyzed. Methods: The fibroblasts from anterior and posterior sclera of two healthy donors were cultured separately. Proteins were extracted from the cell lines, run on 2-DE, and stained by Commassie blue R-250. The gel images were analyzed to detect differences in expression levels (at least a fivefold difference in intensity) and location of the protein spots between the anterior and posterior sclera. These protein spots were trimmed from the gels, digested with trypsin, identified by MALDI mass spectrometry, and functionally categorized with human cDNA and protein databases from NCBI. Results: The number of spots detected was 455 and 453 protein spots from the anterior and posterior scleral fibroblasts, respectively. The patterns of gel maps were very similar between the anterior and posterior sclera in each donor and between the donors in either the anterior or posterior sclera. Nine proteins showed a stronger expression in the anterior sclera compared with the posterior sclera. These proteins together with the two proteins that appeared only in the anterior sclera were mainly associated with anabolic metabolism in cells. Eight proteins showed a stronger expression in the posterior sclera, and seven of them were mainly associated with catabolic metabolism in cells. Among all 19 protein spots identified as being differentially expressed between fibroblasts originally isolated from the anterior or posterior sclera, 14 proteins had a pI (3.86-7.95) and molecular weight (23-66 kDa) consistent with those found in human from the database of NCBI and from SwissProt Entry Name. Conclusions: The distribution and levels of expression in proteins are very similar for both the anterior and posterior sclera in vitro, with only approximately 4% of the proteins demonstrating a differential level of expression (at least fivefold) between the two segments of the sclera. [ABSTRACT FROM AUTHOR]

Purpose : The aim of this study was to identify the presence of muscarinic acetylcholine receptors (mAChRs) in human sclera in order to determine whether the sclera is a potential site of action for mAChR antagonists. Methods : Cell lines of human scleral fibroblasts were cultured in Dulbecco modified Ealge's medium. Reverse transcription–polymerase chain reaction (RT-PCR) and Northern blot analysis were used to detect mRNA expression of muscarinic acetylcholine receptors in the cell lines of the fibroblasts. Western blot analysis and immunocytochemistry were used to detect proteins of mAChRs in the cell lines. Immunohistochemical study was used to further detect the presence of mAChR proteins in the frozen scleral sections. Results : The cultured fibroblasts demonstrated mRNA expression of five mAChRs (m1 to m5) in RT-PCR and Northern blot analysis. The molecular size of mRNA expression was largest for the m3 receptor, followed by the m2, m4, m5, and m1 in both RT-PCR and Northern blot analysis. Proteins of the m1 to m5 receptors were present in cell line fibroblasts under Western blot analysis and immunocytochemistry with a range of molecular weight from 80 kDa (m5) to 60 kDa (m1) in Western blot analysis. The presence of these five receptors was also detected in scleral tissues with immunohistochemistry. Conclusions : This study demonstrated the presence of mAChR subtypes (m1 to m5) in human scleral fibroblasts at both mRNA and protein levels. This finding indicates that the sclera is a potential site of action for the currently used mAChR antagonists in prevention of human myopia. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Retinal bipolar cells (BCs) connect with photoreceptors and relay visual information to retinal ganglion cells (RGCs). Retina-specific deletion of Lhx4 in mice results in a visual defect resembling human congenital stationary night blindness. This visual dysfunction results from the absence of rod bipolar cells (RBCs) and the loss of selective rod-connecting cone bipolar cell (CBC) subtypes and AII amacrine cells (ACs). Inactivation of Lhx4 causes the apoptosis of BCs and cell fate switch from some BCs to ACs, whereas Lhx4 overexpression promotes BC genesis. Moreover, Lhx4 positively regulates Lhx3 expression to drive the fate choice of type 2 BCs over the GABAergic ACs. Lhx4 inactivation ablates Bhlhe23 expression, whereas overexpression of Bhlhe23 partially rescues RBC development in the absence of Lhx4. Thus, by acting upstream of Bhlhe23 , Prdm8 , Fezf2 , Lhx3 , and other BC genes, Lhx4 , together with Isl1 , could play essential roles in regulating the subtype-specific development of RBCs and CBCs. • Lhx4 null mice display a visual defect resembling human CSNB • Loss of Lhx4 results in the loss of rod bipolar cells (RBCs) and rod-connecting BCs • Lhx4 regulates cell fate choice of type 2 BCs over GABAergic amacrine cells through Lhx3 • Overexpression of Bhlhe23 partially rescues RBC development in the absence of Lhx4 Dong et al. show that the loss of Lhx4 in mice results in the loss of rod bipolar cells and rod-connecting bipolar cells and in a visual defect resembling human congenital stationary night blindness. Lhx4 , together with Isl1 , acts upstream of Bhlhe23 , Prdm8 , Fezf2 , and Lhx3 to regulate bipolar cell development. [ABSTRACT FROM AUTHOR]

Spectral composition affects emmetropization in both humans and animal models. Because color vision interacts the effects of chromatic defocus, we developed a method to bypass the effects of longitudinal chromatic aberration by placing a spectral filter behind the optics of the eye, using genetic tools. Newborn C57BL/6J (B6) mice were reared in quasi-monochromatic red (410–510 nm) or blue (585–660 nm) light beginning before eye-opening. Refractive states and ocular dimensions were compared at 4, 6, 8, and 10 weeks with mice reared in normal white light. Cre recombinase-dependent Ai9 reporter mice were crossed with Chx10-Cre to obtain Chx10-Cre;Ai9 mice, expressing red fluorescent protein in retinal Cre-positive cells. Ai9 offsprings, with and without Cre, were reared under a normal visual environment. Refraction and axial components were measured as described above. Expression levels of M and S opsin were quantified by western blotting at 10 weeks. Compared with those reared in white light, B6 mice reared in red light developed relative hyperopia, principally characterized by flattening of corneal curvature. Emmetropization was not affected by blue light, possibly because the reduction in vitreous chamber depth compensated for the increase in corneal curvature. Compared with Cre-negative littermates, the refraction and axial dimensions of Chx10-Cre;Ai9 mice were not significantly different at the follow-up timepoints. M opsin levels were higher in Chx10-Cre;Ai9 mice at 10 weeks while S opsin levels were not different. Red light induced a hyperopic shift in mouse refractive development. Emmetropization was not impacted in mice with perturbed color vision caused by intrinsic red-fluorescent protein, suggesting that color vision may not be necessary in mouse emmetropization when other mechanisms are present. [ABSTRACT FROM AUTHOR]