Transducin and melanopsin independent phototransduction in postnatal retinal development

Genetic ablations of rod and cone transducin alpha subunits in the so-called KK mice do not silent the outer retina as we
have found that inner retinal neurons still robustly respond to light. This surprised transducin-independent light
sensitivity does not depend on melanopsin signaling in intrinsically photosensitive retinal ganglion cells. This so-named
“transducin- and melanopsin-independent phototransduction (TMIP)” embodied in the 3K mice apparently works
through an unknown and potentially novel signaling mechanism in retina. We have shown that TMIP-generated light
signal passes through retinal circuit and is capable of driving retinal ganglion cells to confer image-forming vision. We
hypothesize that TMIP occurs in developing and mature rod and/or cone photoreceptors, mediated by visual pigment
and trimeric G-proteins, and indispensable for normal postnatal retinal development. In Aim-1 we will study the cellular
origin of TMIP to determining relative contributions of rod and/or cone as candidate venue where TMIP takes place. In
Aim-2 we will test the involvement of known visual pigments in TMIP, as well as trimeric G-proteins and other candidate
signaling molecules/pathways. Aim-3 is to fully characterize TMIP’s role in light-dependent postnatal retinal
development at times when transducin-dependent conventional phototransduction is yet to emerge. This application
contains novel findings, conceptual, material and methodological innovations. Significance lies in the advancement of
the phototransduction and retinal development fields, with clinical relevance in explaining mysteries concerning
incomplete human achromatopsia involving Gnat2 and Cnga3 mutations.

Grant Number: 5R01EY032898-05
NIH Institute/Center: NIH
Principal Investigator: Ching-Kang Chen