Saravanan Kolandaivelu
West Virginia University Eye Institute, USA
Title: AIPL1, a protein linked with blinding diseases has distinct roles in rod and cone photoreceptor neurons
Biography
Biography: Saravanan Kolandaivelu
Abstract
Retinal photoreceptor neurons are polarized cells with specialized ciliary extensions called outer segments (OS) needed for vision. Modulation of cGMP in the OS by light is essential for our visual perception. Regulation of cyclic GMP (cGMP) in photoreceptors neurons (rod and cones) is controlled by retinal guanylate cyclase (GC), which produce cGMP. Phosphodiesterase 6 (PDE6) is responsible for hydrolyzing cGMP to GMP upon light activation. Previously, we showed that Aryl hydrocarbon receptor Interacting Protein Like-1 (AIPL1), a protein linked with childhood blindness is needed for rod vision. Our studies show that the loss of AIPL1 in rod cells leads to reduced levels of PDE6 and consequent increase in cGMP that is thought to be the culprit behind rapid death of rod photoreceptor cells. The levels of GC, a cyclase needed for synthesis of cGMP in rods remain unaltered. Similar to rods, AIPL1 is needed for cone-mediated visual response. However, in contrast to rods, cones lacking AIPL1 display severe loss of cone PDE6 and GC. The reduction in enzymes mediating cGMP metabolism is accompanied by reduced levels of cGMP. The link between cGMP levels and rod / cone degeneration remains ambiguous and is currently under investigation.