Intracellular mechanisms in rd1 mouse retinal degeneration

Retinitis pigmentosa (RP) is an inherited disorder and the leading cause of visual impairment in the working age population. It is caused by a number of different genetic mutations, all of which cause the rod photoreceptors to degenerate. As the rods become few in numbers, the cones will also begin to die, resulting in total blindness. Since the genetic defects leading to RP are numerous, it would be overwhelming to treat each variation individually. By finding mechanisms related to photoreceptor survival and degeneration which are common to all forms of RP, a more general therapy can be developed. The rd1 mouse is an animal model of RP used to study these processes. Changes in retinal cells as a result of the rd1 mutation are characterized and manipulated using an in vitro system. Paper I describes how the signaling protein Akt is activated in correlation with developmental and pathological cell death and may be part of an endogenous survival program. Paper II investigates the retinal response to the CNTF and BDNF and shows how their own regulation is increased and the signaling proteins Akt, ERK and CREB are activated. Paper III illustrates the protective effects of antioxidant treatment on rd1 photoreceptors. Paper IV investigates the activation of JNK and c-Jun and evaluates their roles in rd1 degeneration. Paper V simulates the rd1 mutation pharmacologically at different ages and shows how intracellular mechanisms are affected by photoreceptor development. Characterizations such as these will help in the development of therapeutic strategies for RP.