This is consistent with ndings that exposure of RPE cells to other oxidative stress inducers such as tbutylhydroperoxide, light irradiation and lipofuscin can trigger RPE apoptosis. Lack of efcient mtDNA repair accelerates accumulation of damaged mtDNA.As damage accumulates, mitochondrial redox function decreases, leading to a vicious cycle of ROS production and mtDNA damage.As a result, mitochondrial function declines, which results in diminished energy production.When the level of energy production drops below the threshold so that mitochondria lose their ability to maintain the membrane potential.ROS represents reactive oxygen species.It is likely that oxidative stress in vivo is chronic and below levels that cause RPE cell death.Therefore, it would be useful to establish a chronic oxidative stress model system of RPE to simulate the in vivo situation.In contrast to the acute models, this model does not affect cell viability while still inducing ROS production.Another concern is that most studies used RPE cell lines to study oxidative stress.Although RPE cell lines offer some advantages as described earlier, they are transformed and may respond differently to oxidative challenge compared to primary RPE and in vivo RPE.Thus, it would be more appropriate to use freshly isolated or primarily cultured RPE in the future studies.Using QPCR assay, one can examine the formation of oxidative mtDNA damage and repair kinetics in RPE cells from healthy aged human eye donors as well as early AMD eye donors.Finally, there is a need to dene the critical molecular events involved in oxidative stress induced RPE cell death.The response of these RPE cells to oxidative stress may help reveal the mechanisms and pathways that are involved in the development of AMD.Science. Ophthalmology. Populationbased familial aggregation study.Ophthalmology. Observations in monozygotic twins.In vitro generation of oxygenreactive species.Science. Proc. Nat. Acad. Sci. USA. Se is specically incorporated into proteins in the form of selenocysteine and nonspecically incorporated as selenomethionine in place of methionine.After it was conrmed by numerous studies that selenoproteins andor selenoenzymes were involved in the metabolism of all higher vertebrates.Se compounds at low concentration may have protective anticarcinogenic properties, whereas at higher concentration they can be genotoxic and possibly carcinogenic. Many of them reside in its capability of acting as an antioxidant and disease preventing element.Se, depending upon chemical form, can be a prooxidant toxic agent that can induce DNA damage and cell death.Based on human studies, intakes of gday were established as the maximum safe dietary dose with the no observed adverse effect.An intake of gday resulted in denite occurrence of selenosis. On the other hand a level of about gday was suggested as the minimum requirement, while an intake of gday results in deciency problems. Se enters the food chain through plants, which is taken up from the soil.Se deciency is also linked to the occurrence, virulence, and disease progression of some viral infections. Se has a role in the thyroid hormone metabolism being part of the deiodinase enzyme. Lastly, selenomethionine may generate methylselenol by the enzymatic reaction of methionine, lyase. The insertion of selenocysteine into protein is specied by the UGA codon in mRNA.