Fig. 2.
The structural and functional elements of the retina and the localization of selected genes involved in canine retinal degeneration. a Histologic section of the canine retina showing the highly ordered lamination from the outer (top) to the inner (bottom) retina. The rod and cone photoreceptors that form the outermost layer receive the light stimuli and are nourished by the retinal pigment epithelium (RPE). The outer nuclear layer (ONL) contains the nuclei and cell bodies of the photoreceptors. The inner nuclear layer (INL) contains the nuclei of the secondary neurons (i.e., bipolar, amacrine, and horizontal cells) and the glial Müller cells. The innermost ganglion cell layer (GCL) receives the input from photoreceptors via the bipolar and amacrine cells and transmit the signals to the brain. b Localization of selected genes associated with RDs in dogs. *Indicates the cone photoreceptors. Canine RD genes with unknown retinal localization or ubiquitous expression are not displayed. OS outer segment, IS inner segment. c The retinoid cycle recycles the light-absorbing chromophore. Absorption of a photon (hv) converts 11-cis-retinal bound to opsin (Rho) into all-trans-retinal initiating phototransduction. All-trans-retinal is reduced by photoreceptor retinol dehydrogenase (RDH) to all-trans-retinol and exported to the RPE where it is esterified by lecithin retinol acyltransferase (LRAT), converted to 11-cis-retinol by RPE65, and oxidized to 11-cis-retinal by NAD and a cis-specific retinol dehydrogenase (cis-RDH). 11-cis-retinal is exported back to the OS to again bind to opsin. CRALBP cellular retinaldehyde-binding protein, CRBP cellular retinol-binding protein, IRBP interphotoreceptor matrix retinoid-binding protein. d The phototransduction cascade converts light stimuli to electrical signal. Activated opsin (R*) in the disk membrane activates transducin (G) to G* which in turn activates phosphodies-terase (PDE) to PDE**. PDE** hydrolyzes cGMP, reducing its cytoplasmic concentration which results in closure of cGMP-gated channels in the plasma membrane. This causes hyperpolarization of the photoreceptors leading to signals sent to the downstream neurons. The schematics are modified and reprinted with permission from John Wiley and Sons (Nawrot et al. 2006) (c) and Elsevier Limited (Leskov et al. 2000; Pugh 1999) (d)