The goal of this proposal is to understand molecular mechanisms underlying macular degeneration (MD). Macular degenerations are a phenotypically and genotypically heterogenous group of blinding disorders characterized by central vision loss associated with atrophy of retinal pigment epithelium with or without choroidal neovascularization. Understanding the mechanisms underlying these debilitating diseases will help design therapeutic strategies to delay the onset, slow the progression, prevent or treat the condition. We have identified mutations in two novel genes: (1) Elongation very long-chain fatty acid - 4 (ELOVL4) and (2) C1q and tumor necrosis factor related protein 5 (C1QTN5/CTRP5). These mutations occur in families with early-onset atrophic macular degeneration or Stargardt-like dominant macular degeneration (STGD3) and late-onset autosomal dominant hemorrhagic macular degeneration respectively. We propose to study the mechanisms underlying normal photoreceptor maintenance and how disruptions of these mechanisms result in macular degenerations by focusing on the ELOVL4 and CTRP5 genes and their mutations. For each disease our hypothesis is: (a) the wild type protein is critical for the normal function, and (b) abnormal protein production disrupts the retina. We will also test the hypothesis that nutritional intervention delays or slows the progression of STGD3. We will test these hypotheses using cell culture system and animal models. We chose these two distinct forms of macular degenerations because we believe that they offer a unique opportunity to understand functional roles of the genes involved and, thus, to understand other forms of MD.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Biology and Diseases of the Posterior Eye Study Section (BDPE)
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Chin, Hemin R
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University of California San Diego
Schools of Medicine
La Jolla
United States
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Biswas, Pooja; Naeem, Muhammad Asif; Ali, Muhammad Hassaan et al. (2018) Whole-Exome Sequencing Identifies Novel Variants that Co-segregates with Autosomal Recessive Retinal Degeneration in a Pakistani Pedigree. Adv Exp Med Biol 1074:219-228
Gustafson, Kevin; Duncan, Jacque L; Biswas, Pooja et al. (2017) Whole Genome Sequencing Revealed Mutations in Two Independent Genes as the Underlying Cause of Retinal Degeneration in an Ashkenazi Jewish Pedigree. Genes (Basel) 8:
Duncan, Jacque L; Biswas, Pooja; Kozak, Igor et al. (2016) Ocular Phenotype of a Family with FAM161A-associated Retinal Degeneration. Ophthalmic Genet 37:44-52
Sahu, Bhubanananda; Chavali, Venkata R M; Alapati, Akhila et al. (2015) Presence of rd8 mutation does not alter the ocular phenotype of late-onset retinal degeneration mouse model. Mol Vis 21:273-84
Mandal, Nawajes A; Tran, Julie-Thu A; Zheng, Lixin et al. (2014) In vivo effect of mutant ELOVL4 on the expression and function of wild-type ELOVL4. Invest Ophthalmol Vis Sci 55:2705-13
Tiruvalluru, Mrudula; Ananthathmakula, Prashanth; Ayyalasomayajula, Vajreswari et al. (2013) Vitamin A supplementation ameliorates obesity-associated retinal degeneration in WNIN/Ob rats. Nutrition 29:298-304
Duncan, Jacque L; Roorda, Austin; Navani, Mili et al. (2012) Identification of a novel mutation in the CDHR1 gene in a family with recessive retinal degeneration. Arch Ophthalmol 130:1301-8
Sommer, Jeffrey R; Chavali, Venkata R M; Simpson, Sean G et al. (2012) Cloning, characterization, and expression analysis of the pig (Sus scrofa) C1q tumor necrosis factor-related protein-5 gene. Mol Vis 18:92-102
Cukras, Catherine; Gaasterland, Terry; Lee, Pauline et al. (2012) Exome analysis identified a novel mutation in the RBP4 gene in a consanguineous pedigree with retinal dystrophy and developmental abnormalities. PLoS One 7:e50205
Vasireddy, Vidyullatha; Chavali, Venkata R M; Joseph, Victory T et al. (2011) Rescue of photoreceptor degeneration by curcumin in transgenic rats with P23H rhodopsin mutation. PLoS One 6:e21193

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