Final Report Summary - DROSOERSTRESS (ER Stress and Photoreceptor Degeneration in Drosophila)
It is still not clear, however, how misfolded Rhodopsin 1 (and ER stress) trigger retinal degeneration and which are the IRE1/Xbp1 target genes that mediate this protective effect against photoreceptor degeneration.
Furthermore, important questions need clarification in relation to the role of the UPR in developmental processes and disease. In our research, we addressed these important questions with three specific aims:
Aim 1 – Analysis of the molecular mechanisms required for induction of cell death in the context of ER stress.
Aim 2 – The mechanism of induction of cell protection vs death by Xbp1spliced.
Aim 3 – The developmental role of the UPR during photoreceptor differentiation.
We successfully reached our main goals as initially planned. The results obtained were published (in part) in the paper entitled “Xbp1-Independent Ire1 Signaling Is Required for Photoreceptor Differentiation and Rhabdomere Morphogenesis in Drosophila” by Coelho et al (2013) Cell Reports, 5, 791-801. Other results obtained are still to be published. These results will likely have strong relevance in terms of human health, as ER stress and the activation of the UPR have been described as being important factors not only in Retinitis Pigmentosa but also in other neurodegenerative disorders.