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The role of ipRGCs in ocular growth and myopia development.

ABSTRACT: The increasing global prevalence of myopia calls for elaboration of the pathogenesis of this disease. Here, we show that selective ablation and activation of intrinsically photosensitive retinal ganglion cells (ipRGCs) in developing mice induced myopic and hyperopic refractive shifts by modulating the corneal radius of curvature (CRC) and axial length (AL) in an opposite way. Melanopsin- and rod/cone-driven signals of ipRGCs were found to influence refractive development by affecting the AL and CRC, respectively. The role of ipRGCs in myopia progression is evidenced by attenuated form-deprivation myopia magnitudes in ipRGC-ablated and melanopsin-deficient animals and by enhanced melanopsin expression/photoresponses in form-deprived eyes. Cell subtype-specific ablation showed that M1 subtype cells, and probably M2/M3 subtype cells, are involved in ocular development. Thus, ipRGCs contribute substantially to mouse eye growth and myopia development, which may inspire novel strategies for myopia intervention.

SUBMITTER: Liu AL

PROVIDER: S-EPMC9176740 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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The role of ipRGCs in ocular growth and myopia development.

Liu Ai-Lin AL Liu Yun-Feng YF Wang Ge G Shao Yu-Qi YQ Yu Chen-Xi CX Yang Zhe Z Zhou Zi-Rui ZR Han Xu X Gong Xue X Qian Kang-Wei KW Wang Li-Qin LQ Ma Yuan-Yuan YY Zhong Yong-Mei YM Weng Shi-Jun SJ Yang Xiong-Li XL

Science advances 20220608 23

The increasing global prevalence of myopia calls for elaboration of the pathogenesis of this disease. Here, we show that selective ablation and activation of intrinsically photosensitive retinal ganglion cells (ipRGCs) in developing mice induced myopic and hyperopic refractive shifts by modulating the corneal radius of curvature (CRC) and axial length (AL) in an opposite way. Melanopsin- and rod/cone-driven signals of ipRGCs were found to influence refractive development by affecting the AL and ...[more]

PMID: 35675393

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Project description:PurposeStature at a particular age can be considered the cumulative result of growth during a number of preceding growth trajectory periods. We investigated whether height and weight growth trajectories from birth to age 10 years were related to refractive error at ages 11 and 15 years, and eye size at age 15 years.DesignProspective analysis in a birth cohort.ParticipantsChildren participating in the Avon Longitudinal Study of Parents and Children (ALSPAC) U.K. birth cohort (minimum N = 2676).MethodsGrowth trajectories between birth and 10 years were modeled from a series of height and weight measurements (N = 6815). Refractive error was assessed by noncycloplegic autorefraction at ages 11 and 15 years (minimum N = 4737). Axial length (AXL) and radius of corneal curvature were measured with an IOLMaster (Carl Zeiss Meditec, Welwyn Garden City, U.K.) at age 15 years (minimum N = 2676). Growth trajectories and an allelic score for 180 genetic variants associated with adult height were tested for association with refractive error and eye size.Main outcome measuresNoncycloplegic autorefraction at ages 11 and 15 years, and AXL and corneal curvature at age 15 years.ResultsHeight growth trajectory during the linear phase between 2.5 and 10 years was negatively associated with refractive error at 11 and 15 years (P<0.001), but explained <0.5% of intersubject variation. Height and weight growth trajectories, especially shortly after birth, were positively associated with AXL and corneal curvature (P<0.001), predicting 1% to 5% of trait variation. Height growth after 2.5 years was not associated with corneal curvature, whereas the association with AXL continued up to 10 years. The height allelic score was associated with corneal curvature (P = 0.03) but not with refractive error or AXL.ConclusionsUp to the age of 10 years, shared growth mechanisms contribute to scaling of eye and body size but minimally to the development of myopia.Financial disclosure(s)The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Project description:BackgroundMyopia is the leading cause of visual impairment and affects millions of children worldwide. Timely and annual manual optometric screenings of the entire at-risk population improve outcomes, but screening is challenging due to the lack of availability and training of assessors and the economic burden imposed by the screenings. Recently, deep learning and computer vision have shown powerful potential for disease screening. However, these techniques have not been applied to large-scale myopia screening using ocular appearance images.MethodsWe trained a deep learning system (DLS) for myopia detection using 2,350 ocular appearance images (processed by 7,050 pictures) from children aged 6 to 18. Myopia is defined as a spherical equivalent refraction (SER) [the algebraic sum in diopters (D), sphere + 1/2 cylinder] ≤-0.5 diopters. Saliency maps and gradient class activation maps (grad-CAM) were used to highlight the regions recognized by VGG-Face. In a prospective clinical trial, 100 ocular appearance images were used to assess the performance of the DLS.ResultsThe area under the curve (AUC), sensitivity, and specificity of the DLS were 0.9270 (95% CI, 0.8580-0.9610), 81.13% (95% CI, 76.86-5.39%), and 86.42% (95% CI, 82.30-90.54%), respectively. Based on the saliency maps and grad-CAMs, the DLS mainly focused on eyes, especially the temporal sclera, rather than the background or other parts of the face. In the prospective clinical trial, the DLS achieved better diagnostic performance than the ophthalmologists in terms of sensitivity [DLS: 84.00% (95% CI, 73.50-94.50%) versus ophthalmologists: 64.00% (95% CI, 48.00-72.00%)] and specificity [DLS: 74.00% (95% CI, 61.40-86.60%) versus ophthalmologists: 53.33% (95% CI, 30.00-66.00%)]. We also computed AUC subgroups stratified by sex and age. DLS achieved comparable AUCs for children of different sexes and ages.ConclusionsThis study for the first time applied deep learning to myopia screening using ocular images and achieved high screening accuracy, enabling the remote monitoring of the refractive status in children with myopia. The application of our DLS will directly benefit public health and relieve the substantial burden imposed by myopia-associated visual impairment or blindness.

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The role of ipRGCs in ocular growth and myopia development.

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The role of ipRGCs in ocular growth and myopia development.

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