Treatment Of Age-related Macular Degeneration Patients Research Articles

The Bcl-2/Bcl-xL Inhibitor ABT-263 Attenuates Retinal Degeneration by Selectively Inducing Apoptosis in Senescent Retinal Pigment Epithelial Cells.

Age-related macular degeneration (AMD) is one of the leading causes of blindness in elderly individuals. However, the currently used intravitreal injections of anti-vascular endothelial growth factor are invasive, and repetitive injections are also accompanied by a risk of intraocular infection. The pathogenic mechanism of AMD is still not completely understood, but a multifactorial mechanism that combines genetic predisposition and environmental factors, including cellular senescence, has been suggested. Cellular senescence refers to the accumulation of cells that stop dividing due to the presence of free radicals and DNA damage. Characteristics of senescent cells include nuclear hypertrophy, increased levels of cell cycle inhibitors such as p16 and p21, and resistance to apoptosis. Senolytic drugs remove senescent cells by targeting the main characteristics of these cells. One of the senolytic drugs, ABT-263, which inhibits the antiapoptotic functions of Bcl-2 and Bcl-xL, may be a new treatment for AMD patients because it targets senescent retinal pigment epithelium (RPE) cells. We proved that it selectively kills doxorubicin (Dox)-induced senescent ARPE-19 cells by activating apoptosis. By removing senescent cells, the expression of inflammatory cytokines was reduced, and the proliferation of the remaining cells was increased. When ABT-263 was orally administered to the mouse model of senescent RPE cells induced by Dox, we confirmed that senescent RPE cells were selectively removed and retinal degeneration was alleviated. Therefore, we suggest that ABT-263, which removes senescent RPE cells through its senolytic effect, has the potential to be the first orally administered senolytic drug for the treatment of AMD.

Stem cell-based technologies in treatment of age-related macular degeneration patients: current state of the problem

Age-related macular degeneration (AMD) is the most common disease of the macula the area responsible for central vision. With regard to the pathogenesis of AMD, the main focus of most researchers is on the pathological processes occurring in the retinal pigment epithelium (RPE), which is considered as the main target of the disease. For the treatment of the dry form of the disease, which accounts for about 90% of all AMD cases, up to now no effective treatment methods were elaborated, while in the therapy of the wet form, antiangiogenic therapy, photodynamic therapy, and surgical treatment methods have been used with concrete success. Stem cells, possessing enormous therapeutic potential, are gradually being introduced into medical technologies, including ophthalmology. A number of pre-clinical studies have proven the safety of using cultured cells of the RPE, which gave rise to the beginning of clinical trials of the use of stem cells in the treatment of AMD patients. The review analyzes the data of scientific literature on the current understanding of the pathogenesis of AMD, pathogenetically substantiated therapies, including those using cell-based technologies, prospects and problems of using stem cells in the treatment of AMD patients.

Evaluating choroidal neovascularization in exudative age-related macular degeneration by fluorescein angiography combined with frequency-domain optical coherence tomography

Objective To evaluate the diagnostic value of Heidelberg retinal angiography(HRA) combined with optical coherence tomography (OCT) to detect neovascularization (CNV) in exudative age-related macular degeneration (AMD) patients. Methods This is a cross-sectional study of a series of clinical cases. AMD diagnosis was established by international standard vision chart, Slit lamp microscope, direct or indirect ophthalmoscope examination. A total of 50 eyes (42 cases) of exudative AMD received HRA and frequency domain OCT scan. All 50 eyes received fundus fluorescein angiography (FFA) and frequency-domain OCT simultaneously, and among them 15 eyes also received indocyanine green angiography (ICGA) at the same time. FFA and ICGA were carried out by conventional methods, CNV was localized by real-time Localization technology of frequency domain OCT. In the radial and grid-like section from the areas with strong fluorescence, image acquisition settings are 7 μm fault for each frame, 30° intervals for radialsection, 10 vertical and 10 horizontal scan lines for grid-like section. CNV can be divided into 4 types (typical CNV, partial typical CNV, occult CNV, CNV scarring) according to their boundaries demonstrated in FFA. Based on the features of the OCT images, there were 3 types of integrated image (sub-RPE type, sub-retinal type and mixed type). Results CNV was detected in all 50 eyes. There were 4 eyes (8%) of typical CNV, 11 eyes (22%) of partial typical CNV, 32 eyes (64 %, including 27 eyes of RPE detachment and 5 eyes of passive late leakage) of occult CNV and 3 eyes (6%) of CNV scarring. There were 4 eyes (8%) of sub-RPE type (CNV under the RPE light band) , 16 eyes (32%) of sub-retinal type(interrupted light band of RPE and choroid capillary layer) and 30 eyes (60%) of mixed type of integrated image. Conclusion The image integration technology of the HRA and frequency domain OCT system provide a valuable tool to classify and measure CNV, which will benefit the clinical treatment of AMD patients. Key words: Macular Degeneration/ diagnosis; Choroidal Neovascularization/ diagnosisTomography, optical coherence; Fluorescein angiography; Diagnostic imaging