Abstract
Purpose: :
Some forms of age-related macular disease are characterized by the appearance deposits arising from abnormal extracellular matrix processing and vascular proliferation. The activity of MMP3 and MMP9 is potentiated by prolonged exposure to light This study examines the effects of light of varying spectral composition on the type 2 vascular endothelium growth factor receptor (VEGFR2) and on tissue inhibitors of MMPs (TIMPs).
Methods: :
We examined the retinas of rabbits implanted with a transparent IOL in one eye and a yellow IOL in the other and then exposed to light of different spectral composition over an average time of 2 years. Total RNA was extracted from retinas isolated from the different groups of animals. Levels of mRNA for the genes TIMP1, TIMP2 and VEGFR2 were determined by quantifying PCR products using a PhosphorImager (Fuji).
Results: :
TIMP1/2 and VEGFR2 gene expression levels detected in the retinas exposed to white light were normal. In contrast, exposure to white light lacking the blue band was related to a marked drop in TIMP1 expression, a slight drop in VEGFR2 expression and unaltered TIMP2 expression. When retinas were exposed to blue light the increased expression of all three genes was observed compared to expression patterns produced in response to white light (TIMP1 3-fold, TIMP2 6-fold, VEGFR2 4-fold). This gene up-regulation was reduced by the use of a yellow IOL when the animals were exposed to white light containing a high percentage of blue light.
Conclusions: :
The up-regulation of the genes coding for TIMPs and VEGFR2 produced after exposure to blue light suggests that the blue region of the light spectrum plays a direct role in the etiology of macular degeneration and that these changes induced by light could be prevented using an IOL that blocks blue light.
Keywords: age-related macular degeneration • gene/expression • neuroprotection