Fluctuations of Sex Steroid Hormone Could be Culprit in Age-Related Macular Degeneration

Gender-based differences may influence several ocular conditions, suggesting that fluctuations in sex steroid homeostasis may have direct effects on eye physiology and the pathogenesis of conditions like Age-Related Macular Degeneration (AMD).

A novel Investigation conducted by a team of scientists, lead by Dr. Antonio Giordano, Director of the Sbarro Institute at Temple University, and Dr. Marcella Macaluso, Director of the Cancer Genetics & Epigenetics Program, Sbarro Institute, explored the effect of sex steroid hormone fluctuations in affecting the physiology of human male retinal-pigment epithelial cells (RPEs).

The study was published online on January 16 in the Journal of Cellular Physiology. The study was funded in part by a grant from the Ken and Ann Douglas Charitable Foundation.

AMD is a multifactorial, progressive disease of the eye characterized by progressive degeneration of the retina, resulting in permanent damage to central vision among the elderly. AMD has been associated with several factors and conditions including aging, obesity, family history, diet, hypertension, arteriosclerosis, and hypercholesterolemia. However, despite intensive basic and clinical research, AMD pathogenesis remains unclear, probably due to the multifactorial characteristics of this disease. Of particular interest is the controversial link between AMD and gender.

“To mimic sex steroid hormone fluctuations occurring with aging, we exposed retinal pigment epithelial cells, ARPE-19, to acute, prolonged or chronic estradiol and progesterone challenges,” says Carlo Astarita, PhD, University of Siena and co-author of the study. “We found that chronic estradiol treatment induces cell death of RPEs via necrosis, through mechanisms involving the subcellular localization of the retinoblastoma-related protein pRb2/p130 and the extracellular plasminogen activator inhibitor type-2, PAI-2.”

Moreover, study authors Dr. Macaluso and Dr. Giordano conclude: “This study has high clinical significance since it considers sex steroid fluctuations as inducers of milieu changes in the retina that are able to influence pathological situations occurring with aging in non-reproductive systems such as the eye.”

“Today, the mechanisms governing the action of sex steroid hormones in maintaining the health of the eye are still largely unknown and our investigation offers the unique opportunity to unravel the effects of sex hormones,” says Dr. Mina Massaro-Giordano, co-author of the study and Professor of Ophthalmology at Hospital of the University of Pennsylvania, “not only in determining gender differences, but also in affecting the physiology of non-reproductive systems, such as the eye.”