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Published on: October 24, 2013
Reprogramming of adult rod photoreceptors prevents retinal degeneration
Cynthia L Montana1, Alexander V Kolesnikov, Susan Q Shen
1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Abstract:
A prime goal of regenerative medicine is to direct cell fates in a therapeutically useful manner. Retinitis pigmentosa is one of the most common degenerative diseases of the eye and is associated with early rod photoreceptor death followed by secondary cone degeneration. We hypothesized that converting adult rods into cones, via knockdown of the rod photoreceptor determinant Nrl, could make the cells resistant to the effects of mutations in rod-specific genes, thereby preventing secondary cone loss. To test this idea, we engineered a tamoxifen-inducible allele of Nrl to acutely inactivate the gene in adult rods. This manipulation resulted in reprogramming of rods into cells with a variety of cone-like molecular, histologic, and functional properties. Moreover, reprogramming of adult rods achieved cellular and functional rescue of retinal degeneration in a mouse model of retinitis pigmentosa. These findings suggest that elimination of Nrl in adult rods may represent a unique therapy for retinal degeneration.
Insights
Scientists reprogrammed adult rod cells into cone cells by inhibiting the NRL gene. This cell conversion rescued retinal degeneration in a mouse model, offering a potential therapy for retinitis pigmentosa.
Area of Science:
- Regenerative Medicine
- Ophthalmology
- Molecular Biology
Background:
- Retinitis pigmentosa causes progressive vision loss due to photoreceptor degeneration.
- Early rod cell death in retinitis pigmentosa leads to secondary cone cell loss.
Purpose of the Study:
- To investigate if adult rod photoreceptors can be converted into cone cells.
- To determine if inhibiting NRL can prevent secondary cone degeneration in retinitis pigmentosa models.
Main Methods:
- Engineered a tamoxifen-inducible Nrl allele for acute gene inactivation in adult rod cells.
- Analyzed molecular, histologic, and functional changes post-Nrl knockdown.
Main Results:
- Inactivation of Nrl reprogrammed adult rod cells to exhibit cone-like characteristics.
- This reprogramming rescued cellular and functional deficits in a mouse model of retinitis pigmentosa.
Conclusions:
- Eliminating Nrl in adult rods can convert them into cone-like cells.
- This cell fate reprogramming shows promise as a novel therapeutic strategy for retinal degeneration.
