Table of Contents
Discovery and Background
Retinitis pigmentosa (RP) refers to a category of diseases characterized by incremental retinal degeneration. This damage typically starts in the mid-periphery of the retina and advances towards the macula and later, the fovea. Predominant symptoms of RP are night blindness, which develops from mild to acute, followed by diminishing visual fields, tunnel vision, and ultimately legal or total blindness (Ferrari et al., 2011). At the cellular level, these degenerative symptoms correlate with a considerably impaired rod photoreceptor system. In advanced phases, the disease may damage the cone photoreceptor, culminating in total blindness. These diseases photoreceptors go through apoptosis, which is evident from the reduced thickness of nuclear in the retina. There are also lesions and retinal pigment formations in the fundus. This implies that RP patients could lose a large proportion of photoreceptors prior to undergoing loss of visual acuteness. According to Ferrari et al. (2011), the clinical indicators of RP include an anomalous fundus with constricted retinal vessels and bone-spicule deposits, anomalous, reduced or lacking a- and b- waves in the electroretinogram (ERG), as well as, limited visual spectrum. Symptoms usually begin in early adolescence and acute visual impairment occurs between the ages 40 and 50. In regard to epidemiology, RP prevalence is approximately one individual in every 4000 and the disease is broadly delineated to include syndromic retinitis pigmentosa and non-syndromic retinitis pigmentosa.
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Diagnosis and Current Treatments
Clinical diagnosis of RP is based on the incidence of night blindness and marginal defects of a patient’s visual field, fundus lesions, traces of hypovolted ERG, and progression of these symptoms. A comprehensive ERG is the primary diagnostic tool, especially when patients are not showing symptoms during early stages of the disease, when the fundus appears normal. The ERG is also critical to diagnosis in autosomal dominant forms characterized by variable penetrance, because it is typically hypovolted prior to emergence of clinical symptoms like night blindness. Presently a methodical molecular diagnosis is not widely used, as a result of the significant genetic heterogeneity of RP.
There is currently no therapy that stops the progression of retinal damage or one that aids in restoration of vision. Nonetheless, there are some therapeutic regimens meant to slow down the degeneration process and treating emergent complications, while helping individuals cope with socio-psychological effects of vision loss. In regard to slowing down degeneration, there are therapy strategies such as light protection and vitamin-therapy. Patients suffering pigmentary retinopathies are partially light-dependent, hence the recommendation to put on dark glasses outdoors. In addition, doning yellow-orange glasses reduced photophobia. Overall, lateral protection and eyeshade minimizes the negative impact of light rays. Vitamin therapy, on the other hand, particularly Vitamin A supplementation at a dosage of 15,000 units daily has been reported to minimize ERG amplitude loss. In regard to emergent complications, treatment primarily addresses macular edema and cataract. For the former, conventional treatment involves use of carboanhydrase inhibitors like acetazolamide sodium with daily dosage of not more than 500 mg. For cataract, phacoemulsification with intraocular lens implantation of intraocular lens is required.
Future Directions and Clinical Trials
It is evident from the preceding section that current RP treatments are limited. However, there are several advances poised to enhance the field. Some of these prospective treatments include gene therapy, stem cells transplantation, electronic retina implantation, and pharmacological therapy (Lin, Yi-Ting & Tsang, 2015). Gene therapy makes use of designed viruses to inject normal genes into a patient’s cells. This is a potent approach to treating genetic diseases characterized by recessive mutations where no functional proteins are produced. As highlighted by Waseem et al. (2007), even though visual functionality improvements were sustained for some RP patients who got gene therapy treatment in a startup trial, a follow-up research carried out by one of the three original groups found that there was continuing death of photoreceptors in the treated retinas. On the other hand, in trials carried out on dogs, gene therapy was successful in maintaining visual functionality and preventing degeneration of photoreceptors, when the viruses were inserted prior to the start of photoreceptor loss. The researchers suggest that the findings are indicative of the possibility of reversing degeneration, as long as it is at the early phases of the disease before occurrence of photoreceptors (Waseem et al. 2007). In line with this theoretical concept, gene therapy could only prevent degeneration in youths yet to show clinical symptoms of photoreceptor loss.
While gene therapy treatment would aid in correcting the genetic disease in extant cells, cell-based treatment is a potent option which could help in replacement of cells lost as the disease progresses. This brings to light the potential in stem-cell transplantation. Although ethically controversial, due to possibilities of infection and concerns about quality control, improved technologies of cell manipulation could facilitate transplantation of cultured retinal cells as a viable RP treatment option (Lin et al., 2015).
For individuals at the final stage of retinal disease, there is potential in using an electronic retina implant. The device, which comprises of a camera attached to spectacles and an electrode array helps transmit wireless signals to the retinal neural circuit. As result, the device provides visual perception, albeit limited (Lin et al., 2015) Regarding pharmacological therapy, further research is necessary into neurotrophic or local growth factors that are generated by rods and peripheral cells, which could aid survival of photoreceptors. One example of these factors that wield this potential is the Ciliary neurotrophic factor (CNTF), which promotes cone survival (Barragan et al., 2008).
In addition to the previous potential treatments, there are several clinical trials currently underway, all aimed at looking for effective RP treatments. One such clinical trial is by Ocata Therapeutics (Marlborough, MA). The study provides results of two studies in progress, involving use of embryonic stem (ES) cell-derived RPE cells in treatment of retinal degeneration in Stargardt and AMD patients. At the time of reporting, there had been no adverse effects stemming from transplantation like tumor formation or rejection. Nonetheless, the researchers had observed adverse effects of immunosuppression and subretinal injection (Bainbridge et al., 2008).
Another notable clinical trial is by StemCells Inc., a company located in Palo Alto, California. The company reported transplanting neural progenitor cells derived from embryo stem into patients suffering from AMD. There are several other institutions focusing on stem-cell therapy as a treatment option for retinal degenerative disorders like RP. An example is the California Institute for Regenerative Medicine, which is financing several projects to develop RP therapy with the use of ES cell-obtained retinal progenitor cells. However, FDA approval is yet to be granted on the outcomes of preclinical efficacy and safety assessments.
- Bainbridge, J., Smith, A., Barker, S., Robbie, S., Henderson, R., Balaggan, K.,… & Viswanathan, A. (2008). Effect of gene therapy on visual function in Leber’s congenital amaurosis. New England Journal of Medicine, 358(21):2231–2239.
- Barragan, I., Abd El-Aziz, M., Borrego, S., El-Ashry, M., O’Driscoll, C., Bhattacharya, S., & Antinolo, G. (2008). Linkage validation of RP25 using the 10K GeneChip array and further refinement of the locus by new linked families. Annual Human Genetics, 72(4):454–462.
- Ferrari, S., Di Lorio, E., Barbaro, V., Ponzin, D., Sorrentino, F., & Parmeggiani. (2011). Retinitis Pigmentosa: Genes and Disease Mechanisms. Current Genomics, 12(4): 238–249.
- Lin, M., Yi-Ting, T., & Tsang, S. (2015). Emerging Treatments for Retinitis Pigmentosa Genes and stem cells, as well as new electronic and medical therapies, are gaining ground. Retin Physician, 12: 52–55.
- Waseem, N., Vaclavik, V., Webster, A., Jenkins, S., Bird, A., & Bhattacharya, S. (2007). Mutations in the gene coding for the pre-mRNA splicing factor, PRPF31, in patients with autosomal dominant retinitis pigmentosa. Invest. Investigative Ophthalmology and Visual Science, 48(3):1330–1334.