Retinal dystrophies are a very broad group of complex genetic diseases that lead sequentially, and with variable rhythm and distribution, to the loss of function of the rods (night vision) and/or cones (day, color and central vision). We are in fact endowed with a dual visual system that enables us to adapt to different levels of luminance.
These disorders are the consequence of multiple mutations whose modes of transmission have long been known: dominant, recessive, X-linked, mitochondrial, complex.
The understanding of these diseases, which was made difficult by the extremely late and rare nature of histopathological studies, has benefited greatly from analyses of animal models and, above all, from a better understanding of the molecular physiology of vision. Indeed, the identification first of rhodopsin, then of cone opsins and the many proteins involved in visual phototransduction, as well as the analysis of retinal signalling since the work of Ramón y Cajal, de Wald, Hubel and Wiesel, Dowlilng, Werblin and Nathans, among others, have led to a better understanding of the coding of information in the retina and the mechanisms of visual phototransduction, as well as the structure of photoreceptors.
Based on the analysis of several animal models, new proteins have been identified in the outer segments of photoreceptors, in diseases that are strictly retinal or associated with cochlear or even systemic damage, such as Usher syndrome, or those described in the following seminar.
This has led to the development of a veritable molecular physiology/physiopathology enabling us to better understand the disease. Several deficits have been identified in vitamin A metabolism, renewal of photoreceptor outer segments, all stages of phototransduction and visual adaptation, and synaptic transmission, all of which have led to a better understanding and description of the macromolecular assemblies essential to visual function.
This knowledge has led to the emergence of innovative therapeutic approaches such as gene therapy, which are discussed in other lectures.
