Areas of Interest
Our research focuses on studies of the molecular mechanisms responsible for inherited forms of retinal degeneration causing devastating loss of vision in affected individuals. Our efforts have contributed to the identification of disease genes whose mutations result in early and severe forms of retinal degeneration. Normally these genes are expressed in the retina and retinal pigment epithelium, and encode proteins necessary for the function and survival of the light absorbing rod and cone photoreceptor cells. Disease-associated mutations disrupt cellular processes including the metabolism of vitamin A needed to produce the light-absorbing chromophore 11-cis retinal, the phagocytic uptake of membrane debris from the subretinal space, and the structure and lipid composition of the photoreceptor cells. Our ongoing research focuses on analysis of the normal function and pathogenic mechanisms associated with these genetic defects, in studies involving biochemical assays of protein function and enzyme activity in vitro, and phenotypic characterization of mouse and rat models corresponding to human forms of disease. We are using this information to develop novel strategies for therapeutic intervention that we are testing in preclinical trials.
Honors & Awards
A platform for assessing outer segment fate in primary human fetal RPE cultures.
Zhang Q, Presswalla F, Feathers K, Cao X, Hughes BA, Zacks DN, Thompson DA, Miller JML.
Exp Eye Res. 2019; 178: 212-22.
Inhibiting autophagy reduces retinal degeneration caused by protein misfolding.
Yao J, Qiu Y, Frontera E, Jia L, Khan NW, Klionsky DJ, Ferguson TA, Thompson DA, Zacks DN.
Autophagy. 2018; 14: 1226-38.
Interphotoreceptor retinoid-binding protein removes all-trans-retinol and retinal from rod outer segments, preventing lipofuscin precursor formation.
Chen C, Adler L 4th, Goletz P, Gonzalez-Fernandez F, Thompson DA, Koutalos Y.
J Biol Chem. 2017; 292: 19356-65.
MERTK signaling in the retinal pigment epithelium regulates the tyrosine phosphorylation of GDP dissociation inhibitor alpha from the GDI/CHM family of RAB GTPase effectors.
Shelby SJ, Feathers KL, Ganios AM, Jia L, Miller JM, Thompson DA.
Exp Eye Res. 2015; 140: 28-40.
Deletion of autophagy inducer RB1CC1 results in degeneration of the retinal pigment epithelium.
Yao J, Jia L, Khan N, Lin C, Mitter SK, Boulton ME, Dunaief JL, Klionsky DJ, Guan JL, Thompson DA, Zacks DN.
Autophagy. 2015; 11: 939-53.
Association of Geroprotective Effects of Metformin and Risk of Open-Angle Glaucoma in Persons With Diabetes Mellitus.
Lin HC, Stein JD, Nan B, Childers D, Newman-Casey PA, Thompson DA, Richards JE.
JAMA Ophthalmol. 2015; 133: 915-23.
Advancing therapeutic strategies for inherited retinal degeneration: recommendations from the Monaciano Symposium.
Thompson DA, Ali RR, Banin E, Branham KE, Flannery JG, Gamm DM, Hauswirth WW, Heckenlively JR, Iannaccone A, Jayasundera KT, Khan NW, Molday RS, Pennesi ME, Reh TA, Weleber RG, Zacks DN; Monaciano Consortium.
Invest Ophthalmol Vis Sci. 2015; 56: 918-31.
For a list of publications from MyNCBI, click HERE