Mitochondrial DNA damage in the light-induced retinal degeneration model. Exposure to light causes photoreceptor death. The rate of death depends on many factors, most importantly on the intensity of light and the duration of the exposure. Earlier we described the timecourse of events occuring during exposure to strong (1000Lx) light for 48h hours.  Our findings showed that photoreceptor cell death is present as early as few hours after the exposure started and 12 hours exposure caused major reduction in the photoreceptor population and that the resultant photoreceptor death triggers up-regulation of protective factors in the retina. To investigate further the mechanism of light-induced cell death, we are aiming to identify r early events, including mitochondrial DNA damage.
Krisztina Valter; in collaboration with Prof Silvia Bisti, University of L'Aquila, Italy

Mitochondrial DNA in models of degeneration. Stress resulting from excessive light exposure, abnormal oxygen supply or disease can result in damage to mitochondrial and genomic DNA. Retinal photoreceptors have abundant mitochondria due to their very high metabolic requirements. Mitochondria are also the source of signals that lead to the phenomenon of  ‘programmed cell death’, or apoptosis. Real-time PCR is used to survey damage to mitochondrial and genomic DNA in animal models to identify damage to mitochondrial DNA in the cascade of events leading to apoptosis of photoreceptors.
Krisztina Valter 

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Modelling retinal degeneration
1. The photoreceptor dystrophy of the Royal College of Surgeons (RCS) is known to be driven by a single autosomal recessive mutation which affects the phagocytotic function of the retinal pigment epithelium (PE). The diminished phagocytotic capacity of the PE results in accumulation of subretinal debris. We follow the changes in the photoreceptor cell population and measure the subretinal debris through time in the RCS rat. Adapting an empirically based mathematical model of oxygen flow across the retina (Linsenmeier et al. 2000) we explore the possibility that hypoxia in the early stage of RCS dystrophy can be explained as the result of a retinal detachment caused by the debris formation.
2. It has been shown previously that choroidal denervation results in significant vascular growth in the choroid, suggesting that this model may approximate the conditions resulting in human aged-related macular degeneration (Steinle et al. 2002). In this project, we assess this novel model to verify its potential in AMD research. Our hypothesis is that the increased choroidal vascularization may lead to subretinal fluid accumulation causing a separation between the outer retina and the choroid resulting a significant hypoxia in photoreceptor population, thereby leading to their death. If proven, this model could be used to test new therapeutic measures for AMD sufferers.
Krisztina Valter in collaboration with Prof Silvia Bisti, University of L'Aquila, Italy

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