Related Research Articles
The National Eye Institute (NEI) is part of the U.S. National Institutes of Health (NIH), an agency of the U.S. Department of Health and Human Services. The mission of NEI is "to eliminate vision loss and improve quality of life through vision research." NEI consists of two major branches for research: an extramural branch that funds studies outside NIH and an intramural branch that funds research on the NIH campus in Bethesda, Maryland. Most of the NEI budget funds extramural research.
Macular degeneration, also known as age-related macular degeneration, is a medical condition which may result in blurred or no vision in the center of the visual field. Early on there are often no symptoms. Over time, however, some people experience a gradual worsening of vision that may affect one or both eyes. While it does not result in complete blindness, loss of central vision can make it hard to recognize faces, drive, read, or perform other activities of daily life. Visual hallucinations may also occur.
Lipofuscin is the name given to fine yellow-brown pigment granules composed of lipid-containing residues of lysosomal digestion. It is considered to be one of the aging or "wear-and-tear" pigments, found in the liver, kidney, heart muscle, retina, adrenals, nerve cells, and ganglion cells.
Choroideremia is a rare, X-linked recessive form of hereditary retinal degeneration that affects roughly 1 in 50,000 males. The disease causes a gradual loss of vision, starting with childhood night blindness, followed by peripheral vision loss and progressing to loss of central vision later in life. Progression continues throughout the individual's life, but both the rate of change and the degree of visual loss are variable among those affected, even within the same family.
Stargardt disease is the most common inherited single-gene retinal disease. In terms of the first description of the disease, it follows an autosomal recessive inheritance pattern, which has been later linked to bi-allelic ABCA4 gene variants (STGD1). However, there are Stargardt-like diseases with mimicking phenotypes that are referred to as STGD3 and STGD4, and have a autosomal dominant inheritance due to defects with ELOVL4 or PROM1 genes, respectively. It is characterized by macular degeneration that begins in childhood, adolescence or adulthood, resulting in progressive loss of vision.
Ranibizumab, sold under the brand name Lucentis among others, is a monoclonal antibody fragment (Fab) created from the same parent mouse antibody as bevacizumab. It is an anti-angiogenic that is approved to treat the "wet" type of age-related macular degeneration, diabetic retinopathy, and macular edema due to branch retinal vein occlusion or central retinal vein occlusion.
Pegaptanib sodium injection is an anti-angiogenic medicine for the treatment of neovascular (wet) age-related macular degeneration (AMD). It was discovered by NeXstar Pharmaceuticals and licensed in 2000 to EyeTech Pharmaceuticals, now OSI Pharmaceuticals, for late stage development and marketing in the United States. Gilead Sciences continues to receive royalties from the drugs licensing. Outside the US pegaptanib is marketed by Pfizer. Approval was granted by the U.S. Food and Drug Administration (FDA) in December 2004.
Choroidal neovascularization (CNV) is the creation of new blood vessels in the choroid layer of the eye. Choroidal neovascularization is a common cause of neovascular degenerative maculopathy commonly exacerbated by extreme myopia, malignant myopic degeneration, or age-related developments.
Bestrophin-1 (Best1) is a protein that, in humans, is encoded by the BEST1 gene.
Hemicentin-1 is a protein that in humans is encoded by the HMCN1 gene.
Age-related maculopathy susceptibility protein 2, is a mitochondrial protein that in humans is encoded by the ARMS2 gene.
DARPins are genetically engineered antibody mimetic proteins typically exhibiting highly specific and high-affinity target protein binding. They are derived from natural ankyrin repeat proteins, one of the most common classes of binding proteins in nature, which are responsible for diverse functions such as cell signaling, regulation and structural integrity of the cell. DARPins consist of at least three, repeat motifs or modules, of which the most N- and the most C-terminal modules are referred to as "caps", since they shield the hydrophobic core of the protein. The number of internal modules is indicated as number while the caps are indicated with "N" or "C", respectively. The molecular mass of e.g. 14 or 18 kDa (kilodaltons) for four- (N2C) or five- (N3C) repeat DARPins is rather small for a biologic.
Retinal gene therapy holds a promise in treating different forms of non-inherited and inherited blindness.
Anti–vascular endothelial growth factor therapy, also known as anti-VEGF therapy or medication, is the use of medications that block vascular endothelial growth factor. This is done in the treatment of certain cancers and in age-related macular degeneration. They can involve monoclonal antibodies such as bevacizumab, antibody derivatives such as ranibizumab (Lucentis), or orally-available small molecules that inhibit the tyrosine kinases stimulated by VEGF: sunitinib, sorafenib, axitinib, and pazopanib.
Geographic atrophy (GA), also known as atrophic age-related macular degeneration (AMD) or advanced dry AMD, is an advanced form of age-related macular degeneration that can result in the progressive and irreversible loss of retinal tissue (photoreceptors, retinal pigment epithelium, choriocapillaris) which can lead to a loss of visual function over time. It is estimated that GA affects over 5 million people worldwide and approximately 1 million patients in the US, which is similar to the prevalence of neovascular (wet) AMD, the other advanced form of the disease.
Elizabeth P. Rakoczy is a Hungarian-born molecular ophthalmologist. She is a professor at the University of Western Australia. She started the molecular ophthalmology department at the Lions Eye Institute. In 2017, Rakoczy was awarded the Florey Medal for her human gene therapy trial to modify viruses for the treatment of wet age-related macular degeneration.
Paul A. Sieving is a former director of the National Eye Institute, part of the U.S. National Institutes of Health. Prior to joining the NIH in 2001, he served on the faculty of the University of Michigan Medical School as the Paul R. Lichter Professor of Ophthalmic Genetics. He also was the founding director of the Center for Retinal and Macular Degeneration in the university's Department of Ophthalmology and Visual Sciences.
Conbercept, sold under the commercial name Lumitin, is a novel vascular endothelial growth factor (VEGF) inhibitor used to treat neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME). The anti-VEGF was approved for the treatment of neovascular AMD by the China State FDA (CFDA) in December 2013. As of December 2020, conbercept is undergoing phase III clinical trials through the U.S. Food and Drug Administration’s PANDA-1 and PANDA-2 development programs.
Pegcetacoplan, sold under the brand name Empaveli, among others, is a medication used to treat paroxysmal nocturnal hemoglobinuria and geographic atrophy of the retina. Pegcetacoplan is a complement inhibitor.
Stem cell therapy for macular degeneration is the use of stem cells to heal, replace dead or damaged cells of the macula in the retina. Stem cell based therapies using bone marrow stem cells as well as retinal pigment epithelial transplantation are being studied. A number of trials have occurred in humans with encouraging results.
References
- ↑ Gelfman, Claire M.; Grishanin, Ruslan; Bender, Kristina Oresic; Nguyen, Aivan; Greengard, Judith; Sharma, Pallavi; Nieves, Julio; Kiss, Szilárd; Gasmi, Mehdi (2021-04-01). "Comprehensive Preclinical Assessment of ADVM-022, an Intravitreal Anti-VEGF Gene Therapy for the Treatment of Neovascular AMD and Diabetic Macular Edema". Journal of Ocular Pharmacology and Therapeutics. 37 (3): 181–190. doi:10.1089/jop.2021.0001. ISSN 1080-7683. PMC 8060718 . PMID 33835848.
- ↑ Grishanin, Ruslan; Vuillemenot, Brian; Sharma, Pallavi; Keravala, Annahita; Greengard, Judith; Gelfman, Claire; Blumenkrantz, Mark; Lawrence, Matthew; Hu, Wenzheng; Kiss, Szilárd; Gasmi, Mehdi (January 2019). "Preclinical Evaluation of ADVM-022, a Novel Gene Therapy Approach to Treating Wet Age-Related Macular Degeneration". Molecular Therapy. 27 (1): 118–129. doi: 10.1016/j.ymthe.2018.11.003 . PMC 6319194 . PMID 30528929.