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R. F. Mullins, E. A. Faidley, J. M. Skeie, M. N. Johnson, J. Huang; Choroidal Endothelial Cells in Macular Degeneration: Gene Expression and Choriocapillaris Dropout Associated With Drusen Density. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4944.
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Age-related macular degeneration (AMD) is a blinding disease affecting the neural retina, RPE and choroid. Choroidal changes in early AMD are important but generally underappreciated. We sought to characterize morphologic and molecular features of the choroid in a series of AMD and unaffected eyes.
Sections of 40 human maculas (n=23 unaffected, n=17 clinically diagnosed with early AMD) were obtained and labeled with Ulex europaeus lectin to assess vascular density, anti-CD45 to quantify leukocytes, and/or anti-C5b-9 terminal complement complex. The number of CD45-positive white blood cells, the vascular lumen density, and the cross sectional area of drusen deposits were quantified in a masked fashion. Measurements were analyzed using Student’s t test and linear regression analysis. In addition, cDNA derived from macular punches of RPE-choroid from 5 early AMD donors and 5 unaffected controls were used in a quantitative PCR array to assess the levels of 84 transcripts with functions in endothelial cell biology.
As expected, drusen density was strongly associated with AMD status (11.7x higher, p<0.005). Choriocapillaris vascular density was reduced by 28% in early AMD and leukocyte numbers were 59% higher in early AMD compared to controls, although these values did not reach statistical significance (p>0.05). Linear regression analysis of drusen area vs. choriocapillaris density reveals that drusen area is negatively correlated with choriocapillaris density (p<0.01), i.e., decreased choriocapillaris vascularity is associated with increasing drusen load. Choriocapillaris loss associated with drusen was observed independent of AMD affection status. Quantitative PCR of 84 endothelial cell molecules showed decreased expression of fibronectin (FN1) and prostaglandin I2 synthase, and increased expression of integrin alpha-v (ITGAV) and superoxide dismutase-1 (SOD1) in RPE-choroid samples of AMD donor eyes (fold change >50%, p value <0.05).
This study supports the concept that vascular changes in the choriocapillaris precede advanced disease in AMD, and may promote the conversion from early to end stage AMD. These changes are accompanied by altered gene expression. Further studies will be needed to determine whether vascular loss is a cause or consequence of subRPE deposits.
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