Developmental Dynamics of the Functional State of the Retina in Mice with Inherited Photoreceptor Degeneration

The standard model system for studies of inherited retinal pathologies consists of C3H mice, which have a mutation in the Pde6b gene. These animals show impairment to the functioning of rod phosphodiesterase, leading to photoreceptor death and complete loss of vision by day 4 of life. C3H mice obtained from Charles River Laboratories – strain C3H/Crl – were found to have an additional mutation in the Gpr179 gene, which leads to impairment to the operation of the transduction cascade of retinal ON bipolar cells. Despite the wide use of C3H/Crl mice as a study system, detailed investigation of the characteristics of the photoreceptor degeneration process has yet to be carried out. The aim of the present work was to study the time dynamics of morphological and functional changes occurring at early age in the retinas of C3H/Crl mice. The control group consisted of wild-type mice, i.e., strain C57Bl/6J. The functional state of the retina was assessed using in vivo electroretinography, with morphological analysis of histological preparations of eye tissues. Retinal responses to light stimulation in C3H/Crl mice were found not to involve any contribution from rods or ON bipolar cells throughout the measurement period, starting from day 18 of life, while cone responses disappeared by day 25. The numbers of photoreceptors and neurons in the inner nuclear layer of the retina in C3H/Crl mice were decreased by day 16 of life and photoreceptors almost completely degenerated by day 25. At the same time, response amplitude and retinal sensitivity in wild-type mice underwent no significant changes at early age. These data suggest a picture of the development of retinal pathology in C3H/Crl mice.