Changes in select redox proteins of the retinal pigment epithelium in age-related macular degeneration.

Abstract:

PURPOSE:To examine changes of select reduction-oxidation (redox) sensitive proteins from human donor retinal pigment epithelium (RPE) at four stages of age-related macular degeneration (AMD). DESIGN:Experimental study. METHODS:Human donor eyes were obtained from the Minnesota Lions Eye Bank and graded using the Minnesota Grading System (MGS) into four stages that correspond to stages defined by the age-related eye disease study (AREDS). Protein content in RPE homogenates was measured using Western immunoblotting with protein-specific antibodies. RESULTS:The content of several antioxidant enzymes and specific proteins that facilitate refolding or degradation of oxidatively damaged proteins increased significantly in MGS stage 3. These proteins are involved in the primary (copper-zinc superoxide dismutase [CuZnSOD], manganese superoxide dismutase [MnSOD], and catalase) and secondary (heat shock protein [HSP] 27, HSP 90, and proteasome) defense against oxidative damage. Additionally, the insulin pro-survival receptor exhibited disease-related upregulation. CONCLUSIONS:The pattern of protein changes identified in human donor tissue graded using the MGS support the role of oxidative mechanisms in the pathogenesis and progression of AMD. The MGS uses nearly identical clinical definitions and grading criteria of AMD that are used in the AREDS, so our results apply to clinical and epidemiologic studies using similar definitions. Results from our protein analysis of human donor tissue helps to explain altered oxidative stress regulation and cell-survival pathways that occur in progressive stages of AMD.

journal_name

Am J Ophthalmol

authors

Decanini A,Nordgaard CL,Feng X,Ferrington DA,Olsen TW

doi

10.1016/j.ajo.2006.12.006

subject

Has Abstract

pub_date

2007-04-01 00:00:00

pages

607-15

issue

4

eissn

0002-9394

issn

1879-1891

pii

S0002-9394(06)01414-0

journal_volume

143

pub_type

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