High levels of oxidative radicals generated by daily light exposure and high metabolic rate suggest that the antioxidant machinery of the retina and retinal pigment epithelium (RPE) is crucial for their survival. DJ-1 is a redox-sensitive protein that has been shown to have neuroprotective function in the brain in Parkinson's disease and other neurodegenerative diseases. Here, we analyzed the role of DJ-1 in the retina during oxidative stress and aging. We induced low-level oxidative stress in young (3-month-old) and old (15-month-old) C57BL/6J (WT) and DJ-1 knockout (KO) mice and evaluated effects in the RPE and retina. Absence of DJ-1 resulted in increased retinal dysfunction in response to low levels of oxidative stress. Our findings suggest that loss of DJ-1 affects the RPE antioxidant machinery, rendering it unable to combat and neutralize low-level oxidative stress, irrespective of age. Moreover, they draw a parallel to the retinal degeneration observed in AMD, where the occurrence of genetic variants may leave the retina and RPE unable to fight sustained, low-levels of oxidative stress.

The Plasmodium falciparum Na ؉ /H ؉ exchanger (Pfnhe-1) locus at chromosome 13 and another locus at chromosome 9 have recently been proposed to influence quinine resistance. Here, we sequenced the ms4760 locus of the Pfnhe-1 gene from 244 P. falciparum isolates collected from five different regions of India. A total of 16 different ms4760 alleles (with one to five DNNND repeats) were observed among these isolates. Interestingly, areas with a high prevalence of chloroquine and sulfadoxine-pyrimethamine resistance showed more Pfnhe-1 DNNND repeats compared to low drug resistance areas. The extent of genetic diversity at the ms4760 locus also varied from one region to another, with expected heterozygosity values ranging from 0.47 to 0.88.

Sorsby Fundus Dystrophy (SFD) is a rare inherited autosomal dominant macular degeneration caused by specific mutations in TIMP3 . Patients with SFD present with pathophysiology similar to the more common Age-related Macular Degeneration (AMD) and loss of vision due to both choroidal neovascularization and geographic atrophy. Previously, it has been shown that RPE degeneration in AMD is due in part to oxidative stress. We hypothesized that similar mechanisms may be at play in SFD. The objective of this study was to evaluate whether mice carrying the S179C -Timp3 mutation, a variant commonly observed in SFD, showed increased sensitivity to oxidative stress. Antioxidant genes are increased at baseline in the RPE in SFD mouse models, but not in the retina. This suggests the presence of a pro-oxidant environment in the RPE in the presence of Timp3 mutations. To determine if the RPE of Timp3 mutant mice is more susceptible to degeneration when exposed to low levels of oxidative stress, mice were injected with low doses of sodium iodate. The RPE and photoreceptors in Timp3 mutant mice degenerated at low doses of sodium iodate, which had no effect in wildtype control mice. These studies suggest that TIMP3 mutations may result in a dysregulation of pro-oxidant—antioxidant homeostasis in the RPE, leading to RPE degeneration in SFD.