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ARRA Investments in Retinal Degeneration

Public Health Burden
Retinal degeneration is a leading cause of blindness in the United States. The disorder is common in elderly people, especially those in developing countries.

Current treatments for retinal degenerative diseases are only marginally effective. High-doses of antioxidant supplements (beta-carotene, vitamins C and E, and zinc) and intravitreal injections of growth factor inhibitors can slow the progression of these disorders, but there is no cure. One recent breakthrough in treating neovascular (wet) age-related macular degeneration is the development of Lucentis and Avastin (off-label use); these drugs are inhibitors of Vascular Growth Factor F. Most patients can maintain vision with monthly intraocular injections, but these treatments are costly and invasive. To lay the basis for future treatments, NIH ARRA funds support basic investigations.

Basic Research
  • Developing an electronic retinal prosthetic device which will attach to the outer wall (sclera) of the eye. The implant stimulates surviving cells in the retina with electrical patterns that will restore a limited but useful level of vision to patients blind from retinal degenerative disease.1
  • Developing a nanoprotein delivery method (nanomedicine) to deliver therapeutic proteins, such as small heat shock proteins, that are known to prevent misfolding and aggregation of proteins linked to several retinal degenerative diseases.2
  • Evaluating the use of cerium oxide nanoparticles to treat inherited retinal degeneration in a mouse model. This reagent has been shown to block the oxidative stress pathway and neuronal cell death associated with loss of retinal activity.3

Gene Therapy
  • Validating a gene therapy approach which will enable differential expression of multiple transgenes expressing blockers of survival factors which support retinal/choroidal neovascularization associated with many retinal diseases. Regulating transgene expression is essential to achieve therapeutic effect and ensure safety in many gene therapy strategies4
  • Developing gene therapy based treatments for retinal degeneration in dog models. This will eventually be used to treat patients with X-linked retinitis pigmentosa.5
  • Using phage phiC31 integrase technology to demonstrate functional recovery in an animal model of retinal degeneration, and thereby offer an alternative or complementary therapy for retinal diseases.6
  • Developing new gene therapy approaches based on using the HSV VP22 protein to translocate the vectors from retinal pigment epithelium (RPE) cells to photoreceptor neurons. If the strategy is effective, it will have significant impact on new treatments for several retinal diseases.7

Molecular Mechanisms
  • Determining the neuroprotective effects of Wnt signaling growth factors on photoreceptor survival and if modifying the pathway can be used as a therapeutic strategy for preventing photoreceptor cell death, an underlying cause of much retinal degeneration.8
  • Identifying the molecular mechanism by which TIMP-3 inhibits retinal/choroidal neovascularization associated with many retinal diseases.9
  • Identifying novel retinal degeneration loci (genes) in fruit flies (Drosophila) and characterizing the effects of their homologs on retinal degenerative diseases in humans.10
  • Continuing to investigate the neuroprotective mechanisms in rat retinas that occur after a brief period of ischemia. This post-conditioning effect will have clinical relevance to preventing ischemic injury in the retina.11
  • Investigating the role of oxidative stress in the rod photoreceptors in retinopathy of prematurity (ROP) pathogenesis by comparing the results from two preclinical trials in rat models.12
  • Continuing to perform comparative proteomic studies on human primary retinal pigment epithelium (RPE) cultures from age-related macular degeneration (AMD) donors to identify additional therapeutic targets of AMD.13

  1. 2R01EY016674-04A1 -- Advanced Engineering Development of a Chronic Retinal Implant, Joseph Rizzo, Carmen Scholz, John Wyatt (MA)
  2. 1RC1EY020361-01 -- Development of Small heat Shock Proteins as Therapeutic Agents in the Eye, Mark J. Petrash (MO)
  3. 1R01EY018724-01A1 -- Prevention of Inherited Retinal Diseases by Therapeutic Rare Earth Nanoparticles, James F. McGinnis (OK)
  4. 1R01EY014991-05 -- VP22 and TAT Mediated Gene Therapy for the CNS, Rajendra Kumar-Singh (MA)
  5. 3R01EY017549-03S1 -- Translational Research for Retinal Degeneration Therapies, Gustavo D. Aguirre (PA)
  6. 1K08EY017024-01 -- Non-Viral Medicated Gene Targeting to the Retina, Daniel C. Chung (PA)
  7. 1R01EY019555-01 -- Differential Regulation of Multiple Transgenes for Treatment of Eye Disease, Kyson X. Chou (NC)
  8. 1R01EY017837-01A1 -- WNT Signaling and Neuroprotection in the Retina, Abigail Hackam (FL)
  9. 1R01EY016490-01 -- Role of TIMP-3 in Ocular Neovascularization, Bela Anand-Apte, Richard Samulski (OH)
  10. 2R01EY008768-14A1 -- Supplement, Molecular Studies of Retinal Degeneration in Drosophila, Nansi J. Colley (WI)
  11. 3R01EY010343-15S1 -- The Role of Adenosine in Retinal Ischemia, Steven Roth (IL)
  12. 1RC1EY020308-01 -- Downregulation of Rod Metabolism in Retinopathy of Prematurity, James D. Akula (NY)
  13. 3R21EY016723-02S1 -- Comparative Proteomics to Study Age-Related Maculopathy, Yetrib Hathout (DC)

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Page Last Updated on June 30, 2018 NIH...Turning Discovery Into Health®