Astra Dinculescu, PhD

Dr. Dinculescu received her Ph.D. in Biochemistry from University of Florida in 2002. She completed her postdoctoral training in the laboratory of Dr. William Hauswirth, one of the pioneers of retinal gene therapy using adeno-associated viral vectors (AAVs). She developed an interest in age-related eye diseases following her discovery that mutant S163R C1QTNF5, associated with late-onset retinal degeneration (L-ORD), generates widespread, prominent deposits, reminiscent of those present in patients (Dinculescu et al., Invest Ophthalmol Vis Sci. 2015). She tested novel capsid-mutant AAV vectors in the retina, uncovered their ability to penetrate retinal layers, and systematically characterized their unique transduction patterns, paving the way for future studies essential for ocular gene-therapy to prevent blindness in retinal degenerative diseases (Petrs-Silva et al., Mol Ther. 2011).

In 2016, she was recognized as an Emerging Vision Scientist by the National Alliance for Eye and Vision Research. In the same year, she established an independently funded research program, primarily focused on developing a treatment to prevent blindness in Usher syndrome type III (USH3), an inherited disorder caused by mutations in the Clarin-1 (CLRN1) gene. In her recent studies, Dr. Dinculescu provided evidence that CLRN1 transcripts display a similar pattern of expression in several distinct species, including humans, concentrating in the inner nuclear layer, specifically in Müller glia (Xu et al., J Pathol. 2020; Dinculescu et al., Int Ophthalmol Clin. 2021). This discovery opens new directions towards future mechanistic and therapeutic studies to prevent vision loss in USH3 patients.

USH syndrome represents the most common genetic cause of combined deafness and blindness, with an estimated prevalence ranging from 4 to 17 cases per 100,000 people worldwide. It results in the progressive loss of the retinal photoreceptors in the eye and the auditory hair cells in the inner ear. Research conducted in our laboratory is mainly dedicated to developing therapeutic strategies for Usher syndrome type III (USH3), a disorder caused by mutations in the CLRN1 gene, leading to progressive hearing loss and retinal degeneration. The biological function of CLRN1 in the retina is currently not understood. Importantly, there are no therapeutic approaches that prevent the loss of light-sensitive photoreceptor neurons in USH3 patients. A major challenge hindering the development of treatments to prevent blindness in this disorder is the lack of models that mimic the human vision loss. For this reason, we are developing new models that will contribute greatly to the advancement of our understanding of this disorder, as well as our ability to treat it. Our goals are to understand the roles of CLRN1 protein in Müller glia and how its omission specifically impacts the postnatal and adult retina, in order to develop safe AAV-based gene-therapy tools for preventing blindness in USH3 patients.

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