The Role of Retinal Connexins Cx36 and Horizontal Cell Coupling in Emmetropization in Guinea Pigs

Abstract

The purpose of this study was to determine whether retinal gap junctions (GJs) via connexin 36 (Cx36, mediating coupling of many retinal cell types) and horizontal cell (HC-HC) coupling, are involved in emmetropization. METHODS.Guinea pigs (3 weeks old) were monocularly form deprived (FD) or raised without FD (in normal visual [NV] environment) for 2 days or 4 weeks; alternatively, they wore a −4 D lens (hyperopic defocus [HD]) or 0 D lens for 2 days or 1 week. FD and NV eyes received daily subconjunctival injections of a nonspecific GJ-uncoupling agent, 18-β-Glycyrrhetinic Acid (18-β-GA). The amounts of total Cx36 and of phosphorylated Cx36 (P-Cx36; activated state that increases cell-cell coupling), in the inner and outer plexiform layers (IPLs and OPLs), were evaluated by quantitative immunofluorescence (IF), and HC-HC coupling was evaluated by cut-loading with neurobiotin.RESULTS. FD per se (excluding effect of light-attenuation) increased HC-HC coupling in OPL, whereas HD did not affect it. HD for 2 days or 1 week had no significant effect on retinal content of Cx36 or P-Cx36. FD for 4 weeks decreased the total amounts of Cx36 and P-Cx36, and the P-Cx36/Cx36 ratio, in the IPL. Subconjunctival 18-β-GA induced myopia in NV eyes and increased the myopic shifts in FD eyes, while reducing the amounts of Cx36 and P-Cx36 in both the IPL and OPL. CONCLUSIONS.These results suggest that cell-cell coupling via GJs containing Cx36 (particularly those in the IPL) plays a role in emmetropization and form deprivation myopia (FDM) in mammals. Although both FD and 18-β-GA induced myopia, they had opposite effects on HC-HC coupling. These findings suggest that HC-HC coupling in the OPL might not play a significant role in emmetropization and myopia development.

Alteration of EIF2 Signaling, Glycolysis, and Dopamine Secretion in Form-Deprived Myopia in Response to 1% Atropine Treatment: Evidence From Interactive iTRAQ-MS and SWATH-MS Proteomics Using a Guinea Pig Model

“…After 2-weeks and 4-weeks FDM, relative myopic shifting of refractive errors, elongation of axial length, and vitreous chamber depths observed in the treated eyes were consistent with published parameters of FDM guinea pigs (Lu et al, 2006;Zhi et al, 2021). However, a larger myopic shift (−11.00 ± 0.75 D) in terms of refractive error was found in a previous study in 4-weeks FDM guinea pigs (Wu et al, 2014).…”

RNA-sequencing analysis reveals the long noncoding RNA profile in the mouse myopic retina

“…RGCs and horizontal cells have been studied under the conditions of emmetropization and myopia progression in animal models. Altered cell-cell coupling by the gap junction protein connexin 36 in horizontal cells in the inner plexiform layer (IPL) has been found to play important roles in emmetropization and FDM in guinea pigs, as the uncoupling agent 18-β-GA induces myopic shifts and FDM decreases total connexin 36 levels and phosphorylation ( Zhi et al, 2021 ). In addition, a recent study showed that stimulation of RGCs expressing neuropsin (OPN5) with violet light prevented experimental myopia in mice ( Jiang et al, 2021 ).…”

“…The retina is a thin layer of complex neural tissue that receives light-stimuli and processes visual signal, and transmitted signal to the sclera. Numerous studies have suggested the retina playing important roles in the pathology in myopia, such as circuiting electrical and chemical synapses ( Zhi et al, 2021 ). Moreover, lncRNAs play pathogenic roles in several retinal diseases, such as the lncRNA XIST and nuclear paraspeckle assembly transcript 1, which play roles in diabetic retinopathy ( Li, 2018 ; Dong et al, 2020 ).…”

Depletion of miR-96 Delays, But Does Not Arrest, Photoreceptor Development in Mice

“…All mice were handled and maintained in the animal facility of the School of Ophthalmology and Optometry at Wenzhou Medical University as authorized by the Institutional Animal Care and Use Committee of Wenzhou Medical University. 51 , 52 All animal experiments were performed in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research.…”