ArticleHuman gene therapy2012
Proinsulin slows retinal degeneration and vision loss in the P23H rat model of retinitis pigmentosa.
Article in Human gene therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- Biodegradable microspheres come into sight: A promising biomaterial for delivering drug to the posterior segment of the eyeball.Materials today. Bio · 2024Review
- Inherited Retinal Dystrophies: Role of Oxidative Stress and Inflammation in Their Physiopathology and Therapeutic Implications.Antioxidants (Basel, Switzerland) · 2022Review
- Possible Role of Insulin-Degrading Enzyme in the Physiopathology of Retinitis Pigmentosa.Cells · 2022Article
- Insulin receptor activation by proinsulin preserves synapses and vision in retinitis pigmentosa.Cell death & disease · 2022Article
- Article
- Delivery Systems of Retinoprotective Proteins in the Retina.International journal of molecular sciences · 2021Review
- Article
- Modulation of GSK-3 provides cellular and functional neuroprotection in the rd10 mouse model of retinitis pigmentosa.Molecular neurodegeneration · 2018Article
- Phenotypic characterization of P23H and S334ter rhodopsin transgenic rat models of inherited retinal degeneration.Experimental eye research · 2018Article
- The molecular and cellular basis of rhodopsin retinitis pigmentosa reveals potential strategies for therapy.Progress in retinal and eye research · 2018Review
- Retinal Vascular Degeneration in the Transgenic P23H Rat Model of Retinitis Pigmentosa.Frontiers in neuroanatomy · 2018Article
- The Prohormone Proinsulin as a Neuroprotective Factor: Past History and Future Prospects.Frontiers in molecular neuroscience · 2018Review
- Article
- Gene therapy approaches for the treatment of retinal disorders.Discovery medicine · 2016Review
- Advances in Gene Therapy for Diseases of the Eye.Human gene therapy · 2016Review
- Prenatal Exposure to Curcumin Protects Rod Photoreceptors in a Transgenic Pro23His Swine Model of Retinitis Pigmentosa.Translational vision science & technology · 2015Article
- Natural Compounds from Saffron and Bear Bile Prevent Vision Loss and Retinal Degeneration.Molecules (Basel, Switzerland) · 2015Review
- A High-Throughput Drug Screening Strategy for Detecting Rhodopsin P23H Mutant Rescue and Degradation.Investigative ophthalmology & visual science · 2015Article
- Article
- Microglia activation in a model of retinal degeneration and TUDCA neuroprotective effects.Journal of neuroinflammation · 2014Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proinsulin has been characterized as a neuroprotective molecule. In this work we assess the therapeutic potential of proinsulin on photoreceptor degeneration, synaptic connectivity, and functional activity of the retina in the transgenic P23H rat, an animal model of autosomal dominant retinitis pigmentosa (RP). P23H homozygous rats received an intramuscular injection of an adeno-associated viral vector serotype 1 (AAV1) expressing human proinsulin (hPi+) or AAV1-null vector (hPi-) at P20. Levels of hPi in serum were determined by enzyme-linked immunosorbent assay (ELISA), and visual function was evaluated by electroretinographic (ERG) recording at P30, P60, P90, and P120. Preservation of retinal structure was assessed by immunohistochemistry at P120. Human proinsulin was detected in serum from rats injected with hPi+ at all times tested, with average hPi levels ranging from 1.1 nM (P30) to 1.4 nM (P120). ERG recordings showed an amelioration of vision loss in hPi+ animals. The scotopic b-waves were significantly higher in hPi+ animals than in control rats at P90 and P120. This attenuation of visual deterioration correlated with a delay in photoreceptor degeneration and the preservation of retinal cytoarchitecture. hPi+ animals had 48.7% more photoreceptors than control animals. Presynaptic and postsynaptic elements, as well as the synaptic contacts between photoreceptors and bipolar or horizontal cells, were preserved in hPi+ P23H rats. Furthermore, in hPi+ rat retinas the number of rod bipolar cell bodies was greater than in control rats. Our data demonstrate that hPi expression preserves cone and rod structure and function, together with their contacts with postsynaptic neurons, in the P23H rat. These data strongly support the further development of proinsulin-based therapy to counteract retinitis pigmentosa.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.