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Myopia is characterized of maladaptive increases in scleral fibroblast-to-myofibroblast transdifferentiation (FMT). Scleral hypoxia is a significant factor contributing to myopia, but how hypoxia induces myopia is poorly understood. Here, we showed that myopia in mice and guinea pigs was associated with hypoxia-induced increases in key glycolytic enzymes expression and lactate levels in the sclera. Promotion of scleral glycolysis or lactate production induced FMT and myopia; conversely, suppression of glycolysis or lactate production eliminated or inhibited FMT and myopia. Mechanistically, increasing scleral glycolysis-lactate levels promoted FMT and myopia via H3K18la, and this promoted Notch1 expression. Genetic analyses identified a significant enrichment of two genes encoding glycolytic enzymes, ENO2 and TPI1. Moreover, increasing sugar intake in guinea pigs not only induced myopia but also enhanced the response to myopia induction via the scleral glycolysis-lactate-histone lactylation pathway. Collectively, we suggest that scleral glycolysis contributes to myopia by promoting FMT via lactate-induced histone lactylation. [Display omitted] • Increasing glycolysis in the sclera induces myopia by enhancing lactate production • Hypoxia upregulates the glycolysis/lactate/histone lactylation cascade in myopia • H3K18la activates transcription of Notch1 , promoting fibroblast-to-myofibroblast • A high-sugar diet induces myopia and enhances experimentally induced myopia Scleral hypoxia is a significant factor contributing to myopia, but how hypoxia induces myopia is poorly understood. Here, Lin et al. uncover a hypoxia-induced glycolysis/lactate/histone lactylation cascade that drives fibroblast-to-myofibroblast transdifferentiation (FMT), resulting in myopia. They demonstrate that the suppression of glycolysis, lactate production, or Notch1 expression can mitigate FMT and myopia development. [ABSTRACT FROM AUTHOR]

In the face of an "epidemic" increase in myopia over the last decades and myopia prevalence predicted to reach 2.5 billion people by the end of this decade, there is an urgent need to develop effective and safe therapeutic interventions to slow down this "myopia booming" and prevent myopia-related complications and vision loss. Dopamine (DA) is an important neurotransmitter in the retina and mediates diverse functions including retina development, visual signaling, and refractive development. Inspired by the convergence of epidemiological and animal studies in support of the inverse relationship between outdoor activity and risk of developing myopia and by the close biological relationship between light exposure and dopamine release/signaling, we felt it is timely and important to critically review the role of DA in myopia development. This review will revisit several key points of evidence for and against DA mediating light control of myopia: 1) the causal role of extracellular retinal DA levels, 2) the mechanism and action of dopamine D1 and D2 receptors and 3) the roles of cellular/circuit retinal pathways. We examine the experiments that show causation by altering DA, DA receptors and visual pathways using pharmacological, transgenic, or visual environment approaches. Furthermore, we critically evaluate the safety issues of a DA-based treatment strategy and some approaches to address these issues. The review identifies the key questions and challenges in translating basic knowledge on DA signaling and myopia from animal studies into effective pharmacological treatments for myopia in children. [ABSTRACT FROM AUTHOR]

Abstract: The ND4 G11778A mutation is the most common mitochondrial DNA mutation leading to Leber''s hereditary optic neuropathy (LHON). Despite considerable clinical evidences, the modifier role of nuclear background and mitochondrial haplotypes in phenotypic manifestation of LHON remains poorly understood. We investigated the effect of these modifiers on bioenergetics in lymphoblastoid cell lines derived from five affected subjects of one Chinese family carrying the G11778A mutation and five Chinese controls. Significant reductions in the activities of complexes I and III were observed in mutant cell lines from the Chinese family, whereas the mutant cell lines from other families carrying the same mutation exhibited only reduced activity of complex I. The reduced activities of complexes I and III caused remarkably higher reductions of ATP synthesis in mutant cell lines from the Chinese family than those from other families. The deficient respiration increased generation of reactive oxygen species. The defect in complex III activity, likely resulting from the mitochondrial haplotype or nuclear gene alteration, worsens mitochondrial dysfunction caused by the G11778A mutation, thereby causing extremely high penetrance and expressivity of optic neuropathy in this Chinese family. Our data provide the first experimental evidence that altered activity of complex III modulates the phenotypic manifestation of LHON-associated G11778A mutation. Thus, our findings may provide new insights into the pathophysiology of LHON. [Copyright &y& Elsevier]

Purpose: To investigate the molecular pathogenesis of Leber''s hereditary optic neuropathy (LHON) in Chinese families. Design: Six Han Chinese families who seem to have maternally transmitted LHON were studied by clinical, genetic, and molecular evaluations. Participants: One hundred twenty-seven subjects from 6 Chinese families with a wide range of age-at-onset and severity of visual impairment. Methods: All subjects underwent clinical examination, genetic evaluation, and molecular analysis of mitochondrial DNA (mtDNA). Main Outcome Measures: The ophthalmologic examinations included visual acuity, visual field examination, visual evoked potentials, and fundus photography. The mtDNA analysis included the polymerase chain reaction (PCR) amplification of entire mtDNA and subsequent sequence determination. Results: Six families exhibited low penetrance of visual impairment, with an average of 10.8%. In particular, 9 (6 males/3 females) of 86 matrilineal relatives in these families exhibited variable severity and age at onset in visual dysfunction. The average age at onset of visual loss was 20 years. Molecular analysis of mtDNA in these families identified the homoplasmic ND5 T12338C mutation and distinct set of variants belonging to the Asian haplogroup F2. The T12338C mutation is only present in the maternal lineage of those pedigrees and not in 178 Chinese controls. This mutation resulted in the replacement of the first amino acid, a translation-initiating methionine with a threonine, shortening 2 amino acids of ND5 polypeptide. The T12338C mutation is also located in 2 nucleotides adjacent to the 3′ end of the tRNALeu(CUN). Thus, this mutation may alter ND5 mRNA metabolism and the processing of RNA precursors. As a result, this mutation impairs respiratory function, leading to visual impairment. Conclusions: Several lines of evidence suggest that the mitochondrial ND5 T12338C mutation is associated with LHON. The tissue specificity of this mutation is likely due to the involvement of nuclear modifier genes. The identification of nuclear modifiers is important for the elucidation of the pathogenic mechanism of LHON and an open avenue for therapeutic interventions. The T12338C mutation should be added to the list of inherited risk factors for future molecular diagnosis. Our findings are helpful for counseling families with LHON. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. [Copyright &y& Elsevier]

Abstract: Background: Leber’s hereditary optic neuropathy (LHON) is a maternally inherited disorder. The purpose of this investigation is to understand the role of mitochondrial haplotypes in the development of LHON associated with ND6 T14484C mutation in Chinese families. Methods: One hundred fourteen subjects from ten Han Chinese families with LHON were studied by the clinical and genetic evaluation as well as molecular and biochemical analyses of mitochondrial DNA (mtDNA). Results: Clinical evaluation revealed that ten families exhibited extremely low penetrance of visual impairment, with an average of 10%. In particular, ten (8 males/2 females) of 114 matrilineal relatives in these families exhibited the variable severity and age-at-onset in visual dysfunction. The average age-of-onset of vision loss was 19 years old. Molecular analysis of mitochondrial DNA (mtDNA) identified the homoplasmic T14484C mutation and distinct sets of variants, belonging to the Asian haplogroups B5b, D4, D4g1b, G3a2, R11, R11a and Z3, respectively. However, there was the absence of secondary LHON-associated mtDNA mutations in these ten Chinese families. Conclusion: The low penetrance of vision loss in these Chinese pedigrees strongly indicated that the T14484C mutation was itself insufficient to produce a clinical phenotype. The absence of secondary LHON mtDNA mutations suggests that these mtDNA haplogroup-specific variants may not play an important role in the phenotypic expression of the T14484C mutation in those Chinese families with low penentrace of vision loss. However, nuclear modifier genes and environmental factors appear to be modifier factors for the phenotypic manifestation of the T14484C mutation in these Chinese families. [Copyright &y& Elsevier]

Purpose: To investigate the role of mitochondrial haplotypes in the development of Leber''s hereditary optic neuropathy (LHON) associated with the ND4 G11778A mutation in Chinese families. Design: Eight Han Chinese families with maternally transmitted LHON were studied using clinical, genetic, and molecular evaluations. Participants: One hundred sixty-seven subjects from 8 Chinese families with a wide age range and severity of visual impairment. Methods: All subjects underwent the clinical and genetic evaluation, as well as molecular analysis of mitochondrial DNA (mtDNA). Main Outcome Measures: The ophthalmologic examinations included visual acuity, visual field examination, visual evoked potentials, and fundus photography. Mitochondrial DNA analysis included the polymerase chain reaction amplification of the entire mtDNA and subsequent sequence determination. Results: Eight families exhibited extremely low penetrance of visual impairment, with the average of 13%. In particular, 14 (12 males and 2 females) of 119 matrilineal relatives in these families exhibited the variable severity and age at onset in visual dysfunction. The average age of onset of vision loss was 17 years. Molecular analysis of mtDNA identified the homoplasimic ND4 G11778A mutation and distinct sets of variants belonging to the Asian haplogroups M8a2, D4g2, B4a1c, B5b, N9a1, D4b2b, C, and M7b1. However, there was an absence of secondary LHON-associated mtDNA mutations in these 8 Chinese families. Conclusions: The extremely low penetrance of vision loss in these 8 Chinese pedigrees strongly indicates that the G11778A mutation was itself insufficient to produce a clinical phenotype. The absence of secondary LHON mtDNA mutations suggest that these mtDNA haplogroup-specific variants may not play an important role in the phenotypic expression of the G11778A mutation in those Chinese families with very low penentrace of vision loss. However, nuclear backgrounds and environmental factors seem to be modifying factors for the phenotypic manifestation of the G11778A mutation in these Chinese families. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. [Copyright &y& Elsevier]

Abstract: Purpose: To demonstrate that high-resolution biometry is possible in mouse eyes in vivo, using real-time OCT with focal plane advancement by a stepper motor. Methods: OCT images of eyes were taken from nine 29-day-old C57BL/6 mice(18 eyes) on two consecutive days. A custom-built real-time OCT instrument with a stepper motor was used to advance the focal plane from the corneal apex to the retina along the ocular axis. The ocular dimensions were determined by advancement of the stepper motor as it displayed on the OCT scan images. Results: OCT images of the entire eye, including the cornea, anterior chamber, lens, vitreous chamber, and retina, were successfully obtained from both eyes of all mice. The measured average corneal thickness from 18 eyes at the age of 29 days was 90.8±4.6μm, anterior chamber depth 707.4±21.4μm, lens thickness 1558.7±18.0μm, vitreous chamber depth 707.4±21.4μm and retinal thickness was 186.9±15.1μm. Total axial length (from the corneal apex to the nerve fiber layer of the retina) was 3003.3±44.1μm. None of them were significantly different if measured on two consecutive days, and no significant differences were found between measurements in the left and right eyes. Conclusion: By focal plane advancement of a real-time OCT instrument through the mouse eye, highly repeatable measurements of the ocular dimensions were obtained. This novel method may be used to study small animal models of normal and abnormal eye development. [Copyright &y& Elsevier]

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Abstract: Purpose: Guinea pigs have been increasingly used as an animal model for experimental myopia. Infant guinea pigs are susceptible to recovery from myopia within 2weeks of form deprivation. This study investigated whether adolescent guinea pigs are susceptible to recovery from myopia after a longer period of form deprivation. Method: Twenty-two guinea pigs (age of 3weeks) were randomly assigned to two groups: MDF (monocularly deprived facemask, n =11) and normal control (free of form deprivation, n =11). All animals underwent biometric measurement (refraction, corneal curvature and axial length) prior to the experiment. Animals in the MDF group wore a facemask that covered the right eye for 4weeks. The MDF was then removed and biometric measurement was performed immediately and at 2, 6, 10 and 14days. The same measurement was performed in the normal control group at time-points matching those of the MDF group. Results: The MDF eyes were approximately 4D more myopic with a greater increase in vitreous length by 0.12mm compared to either the fellow or the normal control eyes after form deprivation (p <0.01). This relative myopia shifted rapidly towards hyperopia within 2days after removal of the MDF, followed by a more gradual recovery. A complete recovery occurred by 6days after removal of the MDF compared to the fellow and normal control eyes (p >0.05). Vitreous length in the MDF eyes slightly reduced within 2days after removal of the MDF and then remained steady. The MDF eyes were similar to both the fellow and normal control eyes in vitreous length (p >0.05) 6days after removal of the MDF. There was no significant difference between the MDF, fellow and normal control eyes in the other axial components during the form deprivation and recovery period. Conclusion: Adolescent guinea pigs are susceptible to recovery from MDF-induced myopia. The refractive recovery is mainly correlated to the inhibited axial elongation of the vitreous chamber of the previously deprived eyes. [Copyright &y& Elsevier]

Abstract: Purpose: This study investigated changes in refraction, corneal curvature, axial components and weight of posterior sclera in guinea pig eyes during the normal development from birth. Methods: Sixty-four guinea pigs were assigned to eight groups (n =8 each). Each group underwent a series of ocular measurements at one of the eight time-points (0, 1, 2, 3, 5, 7, 9 and 11 weeks), including refraction (streak retinoscopy), corneal radius of curvature (CRC; keratometry), anterior segment length (AS: corneal thickness and depth of the anterior chamber), thickness of the crystalline lens (CL), vitreous chamber length (VC; all A-scan ultrasonography) and dry weight of a circular 6mm diameter punch in the posterior sclera (electronic balance). Results of all the measurements were statistically compared between right eye and left eye, male and female and among different age groups. Artifacts of retinoscopy due to small eye artifact were also estimated at different ages. Results: The refraction in guinea pig eyes was +5.22±0.23D (Mean, SE) at birth. This value decreased rapidly during the first 3 weeks followed by a slow decline. The overall decrease in refraction was highly significant from birth to 11 weeks (p <0.001 one way ANOVA). The small eye artifact was approximately 4.00D at birth, which reduced to 2.76D at 11 weeks. The guinea pig eyes were emmetropic by 3 weeks of age when the small eye artifact was taken into account. The CRC (3.24±0.01mm at birth), AS (1.20±0.01mm at birth), CL (2.72±0.03mm at birth) and VC (3.28±0.01mm at birth) increased within the first 3 weeks despite a transient decrease in the CRC within the first week. The increase in CRC, CL and VC continued after 3 weeks, however, the AS remained constant after this age. The increase in VC was better correlated to the decline of hyperopia (R 2 =0.70) than the other components (R 2 =0.33–0.39). Dry weight of the posterior sclera increased linearly from birth (p <0.001 between any two close time-points from 3 to 9 weeks) and had a moderately linear correlation with the VC (R 2 =0.60). There were no significant differences between the right eye and left eye or between male and female in all the measurements. Conclusions: In guinea pigs, the hyperopia present at birth rapidly reduces to emmetropia within the first 3 weeks of age. The emmetropization process in guinea pigs is mainly related to the increase in the vitreous chamber length. This relationship in guinea pigs is similar to that in chickens, tree shrews, primates and humans. The axial development of the vitreous chamber in guinea pigs appears to be associated with tissue growth of the posterior sclera. [Copyright &y& Elsevier]

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]

Abstract: The dorsal nucleus of the vagus nerve plays an integral part in the control of visceral function. The aim of the present study was to correlate structural and chemical changes in the developing nucleus with available data concerning functional maturation of human viscera and reflexes. The fetal development (ages 9 to 26 weeks) of the human dorsal nucleus of the vagus nerve has been examined with the aid of Nissl staining and immunocytochemistry for calbindin and tyrosine hydroxylase. By 13 weeks, the dorsal vagal nucleus emerges as a distinct structure with at least two subnuclei visible in Nissl stained preparations. By 15 weeks, three subnuclei (dorsal intermediate, centrointermediate and ventrointermediate) were clearly discernible at the open medulla level with caudal and caudointermediate subnuclei visible at the level of the area postrema. All subnuclei known to exist in the adult were visible by 21 weeks and cytoarchitectonic differentiation of the nucleus was largely completed by 25 weeks. The adult distribution pattern of calbindin and tyrosine hydroxylase immunoreactive neurons was also largely completed by 21 weeks, although morphological differentiation of labeled neurons continued until the last age examined (26 weeks). The structural development of the dorsal nucleus of the vagus nerve appears to occur in parallel with functional maturation of the cardiovascular and gastric movements, which the nucleus controls. [Copyright &y& Elsevier]

Abstract: We report here the characterization of a four-generation Han Chinese family with Leber’s hereditary optic neuropathy (LHON). This Chinese family exhibited a variable severity and age-at-onset of visual loss. Notably, the average age-at-onset of vision impairment changed from 26years (generation III) to 14years (generation IV), with the average of 18years in this family. In addition, 30% and 50% of matrilineal relatives in generation III and IV of this family developed visual loss with a variability of severity, ranging from blindness to normal vision. Sequence analysis of the complete mitochondrial DNA in this pedigree revealed the presence of the homoplasmic ND4 G11778A mutation and 33 other variants, belonging to the Asian haplogroup D4. Of other variants, the homoplasmic G11696A mutation in the ND4 gene is of special interest as it was implicated to be associated with LHON in a large Dutch family and five Chinese pedigrees with extremely penetrance of visual loss. In fact, the G11696A mutation caused the substitution of an isoleucine for valine at amino acid position 313, located in a predicted transmembrane region of ND4. These imply that the G11696A mutation may act in synergy with the primary LHON-associated G11778A mutation in this Chinese pedigree. [Copyright &y& Elsevier]

Abstract: We report here the characterization of a three-generation Han Chinese family with Leber''s hereditary optic neuropathy (LHON). This Chinese family exhibited high penetrance and expressivity of visual impairment. The average age-of-onset was 19 years in this family. All male and 33% female matrilineal relatives in this Chinese family developed visual loss with a wide range of severity, ranging from blindness to normal vision. Sequence analysis of the complete mitochondrial DNA in this pedigree revealed the presence of the ND4 G11778A mutation and 40 other variants, belonging to the Asian haplogroup D4. The G11778A mutation is present at homoplasmy in matrilineal relatives of this Chinese family. Of other variants, the homoplasmic A15951G mutation is of special interest as it is located adjacent to 3′ end, at conventional position 71 of tRNAThr. The adenine (A71) at this position of tRNAThr, highly conserved from bacteria to human mitochondria, has been implicated to be important for tRNA identity and pre-tRNA processing. In fact, the significant reduction of the steady-state levels in tRNAThr was observed in cells carrying both the A15951G and G11778A mutations but not cells carrying only G11778A mutation. Thus, the A15951G mutation most probably leads to a failure in mitochondrial tRNA metabolism, worsening the mitochondrial dysfunction associated with the primary G11778A mutation. These imply that the tRNAThr A15951G mutation may have a potential modifier role in increasing the penetrance and expressivity of the primary LHON-associated G11778A mutation in this Chinese family. [Copyright &y& Elsevier]

Abstract: Mitochondrial m.14484T>C (MT-ND6) mutation has been associated with Leber's hereditary optic neuropathy. Previous investigations revealed that the m.14484T>C mutation is a primary factor underlying the development of optic neuropathy but is not sufficient to produce a clinical phenotype. However, mitochondrial haplogroups have been proposed to modulate the phenotypic manifestation of the m.14484T>C mutation. Here, we performed the clinical, genetic evaluation and complete mitochondrial genome sequence analysis of 41 Han Chinese pedigrees carrying the m.14484T>C mutation. These families exhibited a wide range of penetrances and expressivities of optic neuropathy. The average ratio between affected male/female matrilineal relatives from 41 families was 2:1. The penetrance of optic neuropathy in these Chinese pedigrees ranged from 5.6% to 100%, with the average of 23.8%. Furthermore, the age-of-onset for optic neuropathy varied from 4 to 44years, with the average of 19.3years. Sequence analysis of their mitochondrial genomes identified distinct sets of polymorphisms belonging to ten Eastern Asian haplogroups, indicating that the m.14484T>C mutation occurred through recurrent origins and founder events. We showed that mitochondrial haplogroups M9, M10 and N9 increased the penetrance of optic neuropathy in these Chinese families. In particular, these mitochondrial haplogroup specific variants: m.3394T>C (MT-ND1), m.14502T>C (MT-ND4) and m.14693A>G (MT-TE) enhanced the penetrance of visual loss in these Chinese families. These data provided the direct evidence that mitochondrial modifiers modulate the variable penetrance and expressivity of optic neuropathy among Chinese pedigrees carrying the m.14484T>C mutation. [Copyright &y& Elsevier]

Abstract: Purpose: To determine corneal biomechanical properties in patients with high myopia. Design: Observational study. Methods: High myopia patients (n =45, age: 37.0±12.6 years) with refractive errors of spherical equivalent (SE) greater than −9.00D were recruited in this study along with healthy subjects (n =90, age: 33.7±12.4 years) with refractive errors of SE ranging from 0D to −3.00D. Only the right eye was studied. Central corneal thickness (CCT) was measured by optical coherence tomography (OCT). Metrics of corneal biomechanical properties, including corneal hysteresis (CH) and corneal resistance factor (CRF), were measured with the Ocular Response Analyzer (ORA). The ORA also determined the values of intraocular pressure (IOPg) and corneal compensated IOP (IOPcc). Results: No significant differences of CCT and CRF were present between the two groups (P =.15 and 0.35 for CCT and CRF, respectively); however, CH in the high myope group was lower than that in the controls (P <.01). IOPg and IOPcc were both significantly higher in the high myopes compared to the controls. In both groups, there were significant correlations between CH and CCT and between CRF and CCT. CH was not significantly correlated with age in either the control group or the high myope group (P >.05). There was a significant correlation between CH and SE when the two groups were combined for analysis. Conclusion: CH, but not CRF, was significantly lower in high myopia patients compared to that in normal subjects. The results indicate that some compromised aspects of the biomechanical properties of cornea may exist in people with high myopia. [Copyright &y& Elsevier]

• Sham surgery made cornea steeper, inducing myopic refractive errors in mice. • Optic nerve crush (ONC) induced myopic or hyperopic shifts with an axial origin. • ONC increased retinal dopamine levels. Higher visual centers could modulate visually-guided ocular growth, in addition to local mechanisms intrinsic to the eye. There is evidence that such central modulations could be species (even subspecies)-dependent. While the mouse has recently become an important experimental animal in myopia studies, it remains unclear whether and how visual centers modulate refractive development in mice, an issue that was examined in the present study. We found that optic nerve crush (ONC), performed at P18, could modify normal refractive development in the C57BL/6 mouse raised in normal visual environment. Unexpectedly, sham surgery caused a steeper cornea, leading to a modest myopic refractive shift, but did not induce significant changes in ocular axis length. ONC caused corneal flattening and re-calibrated the refractive set-point in a bidirectional manner, causing significant myopic (<−3 D, 54.5%) or hyperopic (>+3 D, 18.2%) shifts in refractive error in most (totally 72.7%) animals, both due to changes in ocular axial length. ONC did not change the density of dopaminergic amacrine cells, but increased retinal levels of dopamine and DOPAC. We conclude that higher visual centers are likely to play a role in fine-tuning of ocular growth, thus modifying refractive development in the C57BL/6 mouse. The changes in refractive error induced by ONC are accounted for by alternations in multiple ocular dimensions, including corneal curvature and axial length. [ABSTRACT FROM AUTHOR]