Topographic differential analysis and function of age-related protein expression in the retinal pigment epithelium of Callithrix jacchus

• Applicant: Privatdozent Dr. Michael Böhm
• Subject Area: Ophthalmology
• Term: from 2015 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 278124156

Physiological aging hampers visual function in multifactorial ways. Age-related morphological alterations in the retina, the ascending visual pathway, and the visual cortex have to be considered alongside those in praeretinal structures, such as the cornea and lens. Comparative proteomic analyses of the retinas in macula-bearing marmosets and macula-less rats have identified proteins that are altered with maturation and aging. We discovered four age-regulated proteins that are common to both species: peroxiredoxin (Prx), Parkinson disease (autosomal recessive, early onset) 7 (DJ-1), stathmin (STMN), and beta-synuclein (SCNB). We also found an age-related regulation of those proteins within the ascending visual pathway of rats and monkeys. Those proteins have been not reported in the retina and/or in relation to aging before.The retinal pigment epithelium (RPE) is involved in complex functions associated with visual function and the protection of the retina in forming the retina-blood barrier. Physiological aging of the RPE results in morphological and functional alterations. Several ophthalmological diseases such as age-related macular degeneration (AMD) occur due to pathological changes of the RPE. We suggest that examining the role and function of the RPE in macula-bearing retinas will provide a better understanding of age-related disease, such as the AMD. Established laboratory animals such as mice and rats do not possess a macula, which hampers their use as models for AMD research.We will aim to determine the proteome and genome of the unaffected physiologically aged RPEs of common marmosets (Callithrix jacchus) at different age stages. Then, the localization of identified proteins as well as PRX, DJ1, SNCB, and STMN in the macular region and peripheral region will be scrutinized in prepared whole mounts of the RPE. The role and function of the selected proteins in the human-RPE cell line ARPE-19 will be investigated by analyzing specific and functional markers as well as major signaling pathways. The demographic development of an aging population makes it necessary to increase the amount of scientific research into the macular mechanisms involved in the aging process. A better understanding of aging could yield predictive factors to detect the conversion of physiological aging into pathological conditions.

• DFG Programme: Research Grants