Vision-guided ocular growth in a mutant chicken model with diminished visual acuity

Abstract

Visual experience is known to guide ocular growth. We tested the hypothesis that vision-guided ocular growth is disrupted in a model system with diminished visual acuity. We examine whether ocular elongation is influenced by form-deprivation (FD) and lens-imposed defocus in the Retinopathy, Globe Enlarged (RGE) chicken. Young RGE chicks have poor visual acuity, without significant retinal pathology, resulting from a mutation in guanine nucleotide-binding protein β3 (GNB3), also known as transducin β3 or Gβ3. The mutation in GNB3 destabilizes the protein and causes a loss of Gβ3 from photoreceptors and ON-bipolar cells. (Ritchey et al. 2010)FD increased ocular elongation in RGE eyes in a manner similar to that seen in wild-type (WT) eyes. By comparison, the excessive ocular elongation that results from hyperopic defocus was increased, whereas myopic defocus failed to significantly decrease ocular elongation in RGE eyes. Brief daily periods of unrestricted vision interrupting FD prevented ocular elongation in RGE chicks in a manner similar to that seen in WT chicks. Glucagonergic amacrine cells differentially expressed the immediate early gene Egr1 in response to growth-guiding stimuli in RGE retinas, but the defocus-dependent up-regulation of Egr1 was lesser in RGE retinas compared to that of WT retinas. We conclude that high visual acuity, and the retinal signaling mediated by Gβ3, is not required for emmetropization and the excessive ocular elongation caused by FD and hyperopic defocus. However, the loss of acuity and Gβ3 from RGE retinas causes enhanced responses to hyperopic defocus and diminished responses to myopic defocus.

Visually-Driven Ocular Growth in Mice Requires Functional Rod Photoreceptors

“…Axial lengths of FD cohort were normalized to 4-week-old values (baseline) to eliminate individual variability in eye size due to differences in body size. 61 ''Axial shift'' represents the difference in length between the right and left eye after values had been normalized to baseline. The DA and DOPAC levels across age were normalized to the Gnat1 À/À and WT values obtained at ZT3.…”

Investigating mechanisms of myopia in mice

“…In previous refractive development studies, normalizing for body size has not been needed when wild-type chickens of the same breed or monkeys of the same species were used. One recent example of the importance of considering the relative body size to eye size occurs in the retinopathy, globe enlarged (RGE) chicken which has overall smaller body size, but eyes that are proportionally larger compared to wild-type chickens (Ritchey et al, 2012). Thus, reporting raw values between the wild-type and RGE chickens would leave the impression of a smaller eye in the RGE.…”

“…Thus, reporting raw values between the wild-type and RGE chickens would leave the impression of a smaller eye in the RGE. However, when percent change in axial length is compared, the difference in eye size is significantly larger for RGE chickens (Ritchey et al, 2012). As the evaluation of eye size in mutant mouse models becomes more frequent, special attention needs to be given to overall body size and the normalization of values by comparing baseline values or examining relative differences between strains or eyes.…”

The chick eye in vision research: An excellent model for the study of ocular disease

“…The gene, GNB3 , is expressed in ON-type bipolar cells and both rod and cone photoreceptors (Dhingra et al, 2012). The wild type products aid in the opening of cyclic guanosine monophosphate-gated channels (Ritchey et al, 2012a). Ritchey et al (2010) demonstrated complete absence of the GNB3 protein in rge chicks.…”

“…Globe enlargement in the rge strain allows for study of ocular growth, which is important for understanding emmetropization and certain refractive errors. In fact, Ritchey et al (2012a) used rge mutants to show that emmetropization and increased ocular growth due to form-deprivation and hyperopic defocus using lenses does not require high acuity vision or GNB3 mediated signaling. At the same time, growth responses to myopic defocus appeared to be dependent on visual acuity and/or GNB3 mediated signaling.…”