Therapy options for retinitis pigmentosa

Abstract

Introduction: Retinitis pigmentosa (RP), which occurs about 1 in 4,000 people worldwide, is a hereditary retinal degeneration that leads to legal blindness. The condition is characterized by a degeneration of the photoreceptors caused by a variety of responsible genes. Investigations of photoreceptor cell death in RP have provided clues on potential therapeutic targets. In this article, our current understanding of the mechanisms responsible for photoreceptor cell death is briefly summarized and strategies for preventing or retarding the progression of RP are discussed by specifically focusing on its putative therapeutic options.

Areas covered: The clinical features, genetic backgrounds and molecular basis for photoreceptor cell death in RP are presented. Since the mechanisms for retinal degeneration appear to be extremely complicated, a variety of possible therapeutic targets have been proposed, with some having been applied clinically.

Expert opinion: Because RP is genetically heterogeneous, mechanisms for photoreceptor cell death are known to be complex, partially dependent on individual causative genes. These pathways include oxygen stress, endoplasmic reticulum (ER) stress, increased Ca²⁺ uptake by photoreceptor cells, caspase-dependent and/or -independent pathways of apoptosis, parthanatos (poly-ADP-ribose polymerase-1-dependent cell death), epigenetic factors, neurotrophic factors and autophagy, among others. In order to effectively achieve photoreceptor protection therapy, it is necessary to develop proper combinations of various treatment methods, in addition to creating new gene therapy and cell or tissue replacement strategies.

Keywords::

• AIF
• apoptosis
• calpain
• gene therapy
• iPS cell
• mitochondria
• neuroprotection
• PARP
• photoreceptor
• reactive oxygen stress
• retinitis pigmentosa
• visual prosthesis

Acknowledgments

Thanks to FORTE, Co. Ltd., Tokyo, Japan for English editorial assistance.

Declaration of interest

This work was supported in part by Grant-in-Aid for Scientific Research (C-24592616), Japan Society for the Promotion of Science. The authors declare no conflict of interest and received no payment in preparation of this article.

Notes

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