Deciphering OPN3-Dependent Retinoid Signaling in Human Skin and Its Implications for Blue Light-Induced Lipofuscinogenesis

• Grant number: 26/17160-0
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: December 01, 2026
• End date: November 30, 2027
• Field of knowledge: Biological Sciences - Biophysics - Radiology and Photobiology
• Principal Investigator: Mauricio da Silva Baptista
• Grantee: Maiza Cristina Von Dentz
• Supervisor: Leonardo Vinicius Monteiro de Assis
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Gothenburg, Sweden
• Associated to the scholarship: 26/03408-0 - Blue light and epidermic cells: the role of all-trans retinal and of opsin 3 on lipofuscinogenesis, BP.PD

Abstract

Blue light is considered the second most energetic light in the visible spectrum. In relation to UVA radiation; it penetrates the deeper layers of the skin and can induce oxidative stress and cellular damage. Among the endogenous chromophores involved in these responses, lipofuscin acts as a potent photosensitizer and has been associated with lysosomal dysfunction and impaired autophagy. Blue light response can also be mediated by opsins, GPCR proteins that have a binding site to retinal and act like light-sensors. Our group has demonstrated that retinal- and blue-light-induced lipofuscin accumulation in HaCaT keratinocytes relies on Opsin 3 (OPN3). This reveals an unexpected connection between OPN3 and lipofuscinogenesis in keratinocytes. Because retinal derivatives are known precursors of lipofuscin components as well as key players in opsin function, we hypothesize that OPN3 participates in a functional retinoid-dependent visual cycle in keratinocytes and that blue-light activation via OPN3 promotes lipofuscin accumulation through alterations in retinoid metabolism. To test this hypothesis, we will investigate the existence and functionality of a retinoid visual cycle in human skin models and characterize OPN3-dependent molecular responses to blue light and all-trans retinal (atRAL) treatment. Experiments will be conducted using immortalized and primary human keratinocytes, reconstructed three-dimensional skin cultures, and human skin explants. OPN3 knockdown and knockout models will be combined with transcriptomics, proteomics, and bioinformatic analyses to identify regulatory networks associated with retinoid metabolism, autophagy, and lipofuscin accumulation. The proposed study represents a logical next step, moving from monolayer cell culture to a more physiological reconstructed human epidermis. This internship will provide mechanistic insights into the role of OPN3 in skin photobiology, establish a foundation for understanding how blue light influences skin physiology through retinoid-dependent pathways, and will be an excellent opportunity for the applicant to learn new skin models and bioinformatic analyses. (AU)