The broad, long-term objective of this proposal is to elucidate the structure-function relationships of specific interphotoreceptor matrix (IPM) macromolecules, especially as they relate to supporting the maintenance, health and survival of photoreceptor cells of the retina and retinal pigment epithelium (RPE). During the upcoming grant period, the focus will be on GP147, a prominent glycoprotein in the insoluble IPM, and hyaluronan (HA), recently identified as a component of the insoluble IPM.
The Specific Aims are:
Specific Aim 1 : To test the hypothesis that GP147, identified during the previous grant period as a major glycoprotein in the insoluble IPM of human retina, is differentially synthesized and distributed around rods and cones. Emphasis is on determining the distribution of GP147 in macula and peripheral retina, identifying the cells responsible for its synthesis, the structure of the glycoconjugates and isolation of the GP147 gene.
Specific Aim 2 : To test the hypothesis that the mouse IPM contains a homologue to GP147. Emphasis is on the expression and synthesis of GP147 during retinal development and in the rate of turnover of GP147 in the adult.
Specific Aim 3 : To test the hypothesis that GP147 and hyaluronan (HA), also identified during the previous gant period as a component of the insoluble IPM, form associative interactions. Emphasis is on determining whether GP147 interacts with the IPM through associations with HA.
Specific Aim 4 : To test the hypothesis that photoreceptors and/or the RPE are involved in the synthesis of hyaluronan (HA) present in the insoluble IPM. Emphasis is on the cellular origin and development of IPM HA. Because of the strategic location of the IPM, components of this matrix may be targets for genetic disorders that affect this interface which may include retinal detachment, central serous retinopathy, some forms of macular degeneration and retinitis pigmentosa.
| Chen, Qiuyun; Cai, Shenshen; Shadrach, Karen G et al. (2004) Spacrcan binding to hyaluronan and other glycosaminoglycans. Molecular and biochemical studies. J Biol Chem 279:23142-50 |
| West, Karen A; Yan, Lin; Shadrach, Karen et al. (2003) Protein database, human retinal pigment epithelium. Mol Cell Proteomics 2:37-49 |
| Sakaguchi, Hirokazu; Miyagi, Masaru; Darrow, Ruth M et al. (2003) Intense light exposure changes the crystallin content in retina. Exp Eye Res 76:131-3 |
| Gu, Xiaorong; Meer, Susan Gillette; Miyagi, Masaru et al. (2003) Carboxyethylpyrrole protein adducts and autoantibodies, biomarkers for age-related macular degeneration. J Biol Chem 278:42027-35 |
| Hollyfield, Joe G; Salomon, Robert G; Crabb, John W (2003) Proteomic approaches to understanding age-related macular degeneration. Adv Exp Med Biol 533:83-9 |
| Chen, Qiuyun; Lee, Jung Wha; Nishiyama, Kazutoshi et al. (2003) SPACRCAN in the interphotoreceptor matrix of the mouse retina: molecular, developmental and promoter analysis. Exp Eye Res 76:1-14 |
| Nishiyama, Kazutoshi; Sakaguchi, Hirokazu; Hu, Jane G et al. (2002) Claudin localization in cilia of the retinal pigment epithelium. Anat Rec 267:196-203 |
| Crabb, John W; Miyagi, Masaru; Gu, Xiaorong et al. (2002) Drusen proteome analysis: an approach to the etiology of age-related macular degeneration. Proc Natl Acad Sci U S A 99:14682-7 |
| Sakaguchi, Hirokazu; Miyagi, Masaru; Shadrach, Karen G et al. (2002) Clusterin is present in drusen in age-related macular degeneration. Exp Eye Res 74:547-9 |
| Hollyfield, J G; Rayborn, M E; Nishiyama, K et al. (2001) Interphotoreceptor matrix in the fovea and peripheral retina of the primate Macaca mulatta: distribution and glycoforms of SPACR and SPACRCAN. Exp Eye Res 72:49-61 |
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