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![gene therapy
• under investigation
• to replace the defective protein by using DNA vector (eg, adenovirus, lentivirus)
• Gene therapy was successful in providing the missing protein to a dog with Leger congenital
amaurosis (LCA)
• adeno-associated virus (AAV)
• Briard dog with RPE65 mutations after treatment had 20% of its RPE cells express the
functional protein, thereby allowing the dog to see
• also effective in a mouse model of Leber congenital amaurosis
• Trials have also begun for RP, although currently only for MERTK gene mutation
• problems : wide heterogeneity of defects in RP
• Jacobson et al found that gene therapy is acceptably safe and effective in the extrafoveal retina for
LCA caused by RPE65 mutations; however, no benefit and some risk was noted in treating the fovea.
Age-dependent effects were not evident.[18]
• It is not known which, if any, of the RP forms will show reversibility (even with a nondestructive
reinsertion of the appropriate gene in the appropriate locus with appropriate regulation).](https://image.slidesharecdn.com/nw2016rp02-160831013222/85/Nw2016-retinitis-pigmentosa-16-320.jpg)
Uploaded byNawat Watanachai
Nw2016 retinitis pigmentosa
Retinitis pigmentosa (RP) is a genetic disorder affecting the retina, leading to gradual vision loss that often starts with night blindness and progresses to peripheral vision loss and ultimately blindness. Diagnosis involves various eye tests, with electroretinogram (ERG) being crucial, while management includes pharmacological treatments, surgical interventions, and emerging gene therapy and stem cell solutions. The condition varies significantly in severity and progression between individuals, particularly between males and females.
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Nw2016 retinitis pigmentosa
- 1. Retinitis Pigmentosa :A Brief Nawat Watanachai August 2016
- 2. Retinitis Pigmentosa • Retinitispigmentosa (RP) is • a group of genetic disorders that affect the retina’s ability to respond to light • slow loss of vision • begin with nyctalopia • loss of peripheral vision • blindness • +/- photopsia
- 3. characteristics • hereditary • rateof progression and degree of visual loss varies from person to person • Most RP are legally blind by age 40 • central visual field of less than 20 degrees • XR • males : more often and more severe • females : carry the genes and experience vision loss less frequently.
- 4. Eye Tests • visualfield testing • Most useful for follow-up care • Goldmann (kinetic) perimetry is recommended • Color testing • Commonly, mild blue-yellow axis color defects • Dark adaptation study • Disproportionately reduced contrast sensitivity relative to VA • Genetic subtyping
- 5. Eye Tests • opticalcoherence tomography (OCT) • not useful in diagnosing RP • may help in CME
- 6. Eye Tests • Fluoresceinangiography (FA, FFA) • rarely useful in diagnosing RP • may help in CME
- 7. Eye Tests • Electroretinogram(ERG) • Most critical diagnostic test for RP • Electro-oculogram (EOG) • Not helpful in diagnosing RP • but can identify Best vitelliform macular dystrophy • central macular changes • normal ERG, and abnormal EOG
- 8. Systemic diseases thatrelated to RP • hearing loss and RP • Usher syndrome • Waardenburg syndrome • Alport syndrome • Refsum disease • Kearns-Sayre syndrome • External ophthalmoplegia, lid ptosis, heart block, and pigmentary retinopathy • Abetalipoproteinemia • Fat malabsorption, fat-soluble vitamin deficiencies, spinocerebellar degeneration, and pigmentary retinal degeneration • Mucopolysaccharidoses • Hurler syndrome, Scheie syndrome, Sanfilippo syndrome • Bardet-Biedl syndrome • Polydactyly, truncal obesity, kidney dysfunction, short stature, and pigmentary retinopathy • Neuronal ceroid lipofuscinosis • Dementia, seizures, and pigmentary retinopathy • infantile form is known as Jansky-Bielschowsky disease • juvenile form is Vogt-Spielmeyer-Batten disease • adult form is Kufs syndrome
- 9. management : medical •Acetazolamide • Macular edema (Fishman et al and Cox et al) • oral acetazolamide helps • Topical acetazolamide less helps • Adverse effects: • fatigue, renal stones • loss of appetite, hand tingling • electrolyte imbalance, anemia • steroid for macular edema • may be useful but has not been well studied
- 10. management : medical •Pharmacotherapy? • Fat-soluble vitamins • vitamin A, C, E • Ca-channel blockers • iltiazem • Carbonic anhydrase inhibitors • acetazolamide, methazolamide • Docosahexaenoic acid (DHA) • Lutein, Zeaxanthin • medications with potential adverse effects in RP: • Isotretinoin (Accutane) • Sildenafil (Viagra) • High-dose vitamin E
- 11. management : surgical •cataract • cataract extraction • Retina • retinal implant • gene therapy • stem cell therapy • others : RPE transplantation, surgical growth factors placement
- 12. retinal prosthesis • ARGUSII prosthesis : U of southern california • Alpha IMS • Microsystem-based visual prosthesis (MIVP) • spiral cuff electrode around the optic nerve • implantable miniature telescope • Harvard/MIT retinal implant • artificial silicon retina (ASR) • Photovoltaic retinal prosthesis • Bionic vision australia • dobelle eye • intracortical visual prosthesis
- 13. retinal prosthesis • ARGUSII prosthesis : • U of southern california • 60 electrodes • approved • EU 2011 • US 2013
- 14. retinal prosthesis • AlphaIMS • Tubingen, GER • subretinal prosthesis • collect incident light • transform to electrical signals • stimulate ganglion cells • 1500 electrodes
- 15.
- 16. gene therapy • underinvestigation • to replace the defective protein by using DNA vector (eg, adenovirus, lentivirus) • Gene therapy was successful in providing the missing protein to a dog with Leger congenital amaurosis (LCA) • adeno-associated virus (AAV) • Briard dog with RPE65 mutations after treatment had 20% of its RPE cells express the functional protein, thereby allowing the dog to see • also effective in a mouse model of Leber congenital amaurosis • Trials have also begun for RP, although currently only for MERTK gene mutation • problems : wide heterogeneity of defects in RP • Jacobson et al found that gene therapy is acceptably safe and effective in the extrafoveal retina for LCA caused by RPE65 mutations; however, no benefit and some risk was noted in treating the fovea. Age-dependent effects were not evident.[18] • It is not known which, if any, of the RP forms will show reversibility (even with a nondestructive reinsertion of the appropriate gene in the appropriate locus with appropriate regulation).
- 17. stem cells • Celltransplantation to treat retinal disease (including cells derived from stem cells) • to replace damaged RPE or photoreceptor cells • adult bone marrow–derived stem cells and embryonic stem cells • 2011, Advanced Cell Technology (ACT) • human trial of a stem-cell–derived therapy • for ARMD, Stargardt disease • stem cells were differentiated into cells with an RPE phenotype • PPV • injected under the retina • Initial results demonstrated safety and a trend toward visual improvement in 18 patients over 3-12 months • RPE cell transplants (not derived from stem cells) • placed into the subretinal space to rescue photoreceptors in animal models of RP