- APR3 modulates oxidative stress and mitochondrial function in ARPE-19 cells. [Journal Article]
- FJFASEB J 2018 May 24; :fj201800001RR
- Impairment of retinal pigment epithelial (RPE) cells is considered a key contributor to the development of age-related macular degeneration. Apoptosis-related protein 3 (APR3) was recently discovered...
Impairment of retinal pigment epithelial (RPE) cells is considered a key contributor to the development of age-related macular degeneration. Apoptosis-related protein 3 (APR3) was recently discovered after treatment with all- trans retinoic acid, a pivotal molecule in RPE cells. However, the function of APR3 remains poorly understood. In the present study, we found that APR3 could interact with nuclear factor (erythroid-derived 2)-like 2, which is a regulator of phase II enzymes, and that knockdown of APR3 promoted nuclear factor (erythroid-derived 2)-like 2 nuclear translocation and activated expression of phase II enzymes, which was accompanied by improved redox status and mitochondrial activity. Overexpression of APR3 revealed its mitochondrial localization and induced a robust production of reactive oxygen species that was accompanied by impaired mitochondrial oxygen consumption, complex activity, and lower ATP content, resulting in significant changes in mitochondrial structure, which may contribute to cell apoptosis. High doses of all- trans retinoic acid treatment were found to significantly induce APR3 expression, increase reactive oxygen species levels, and decrease ATP content, which were abolished by knockdown of APR3. These results indicate that APR3 plays a vital role in regulating redox status and mitochondrial activity and thus suggest APR3 might be a potential novel target for study of treatment of age-related macular degeneration.-Li, Y., Zou, X., Gao, J., Cao, K., Feng, Z., Liu, J. APR3 modulates oxidative stress and mitochondrial function in ARPE-19 cells.
- Development of novel drugs for ocular diseases: possibilities for individualized therapy. [Journal Article]
- PMPer Med 2010; 7(4):371-386
- In clinical ophthalmology, new and old drug regimens are available for the treatment of major eye diseases, including potentially blinding conditions, such as glaucoma, and various macular diseases. ...
In clinical ophthalmology, new and old drug regimens are available for the treatment of major eye diseases, including potentially blinding conditions, such as glaucoma, and various macular diseases. In glaucoma, therapeutic treatment mainly deals with control of intraocular pressure at low levels but the clinical courses of patients can be very variable. Very often, specific drug combinations and dosages have to be formulated for individual glaucoma patients. In neovascular age-related macular degeneration, choroidal neovascularization can lead to progressive and irreversible visual impairment if not treated early. In recent years, clinical trials using photodynamic therapy with verteporfin and various anti-VEGF antibodies, such as ranibizumab and bevacizumab, have enhanced the treatment outcomes of neovascular age-related macular degeneration. In diabetic macular edema, intravitreal triamcinolone acetonide and anti-VEGF therapy are effective in some patients. Again, responses to treatment are not uniform in all macular patients. Traditional herbal medicine has long been known to play a role in the practice of personalized formulations in Asia. Potential preventive and therapeutic effects have been claimed in individual eye patients. Meanwhile, advanced technologies in molecular biology have led to identification of genes associated with many eye diseases and development of the concept of individual medicine, in which the genotype of a person can be used as a basis for disease prediction or prophylactic treatments. Moreover, pharmacogenomic studies have demonstrated the association of various genotypes or haplotypes with responses to drug therapies, providing hope for tailormade personalized treatments. The combination of genotypic information with clinical features for the prescription of treatment modes in eye diseases is under vigorous research.
- [Clinical parameters of patients with neovascular age-related macular degeneration : Longterm treatment results of an outpatient clinic]. [Journal Article]
- OOphthalmologe 2018 May 22
- CONCLUSIONS: Despite intensive PRN therapy, visual acuity slowly decreased over time. The mean number of injections was comparable to that of prospective studies. The low number of injections in treatment-year 1 may have been due to a lack of experience with the new treatment agents. The slow decrease in visual acuity in clinical routine as opposed to clinical studies may be attributed to a delay between occurrence of disease activity and treatment.
- Reporting quality of randomised controlled trial abstracts on age-related macular degeneration health care: a cross-sectional quantification of the adherence to CONSORT abstract reporting recommendations. [Journal Article]
- BOBMJ Open 2018 May 22; 8(5):e021912
- CONCLUSIONS: Reporting quality of RCT abstracts on AMD investigations showed a considerable potential for improvement to meet the CONSORT abstract reporting recommendations. Furthermore, word counts of abstracts were identified as significantly associated with the overall abstract reporting quality.
- PREDICTIVE FACTORS FOR PROLIFERATIVE VITREORETINOPATHY FORMATION AFTER UNCOMPLICATED PRIMARY RETINAL DETACHMENT REPAIR. [Journal Article]
- RRetina 2018 May 21
- CONCLUSIONS: Cigarette smoking and macular involvement are significant risk factors predictive of PVR formation after uncomplicated primary retinal detachment repair.
- Blue-light filtering intraocular lenses (IOLs) for protecting macular health. [Review]
- CDCochrane Database Syst Rev 2018 May 22; 5:CD011977
- CONCLUSIONS: This systematic review shows with moderate certainty that there is no clinically meaningful difference in short-term BCVA with the two types of IOLs. Further, based upon available data, these findings suggest that there is no clinically meaningful difference in short-term contrast sensitivity with the two interventions, although there was a low level of certainty for this outcome due to a small number of included studies and their inherent risk of bias. Based upon current, best-available research evidence, it is unclear whether blue-light filtering IOLs preserve macular health or alter risks associated with the development and progression of AMD, or both. Further research is required to fully understand the effects of blue-light filtering IOLs for providing protection to macular health and function.
- Spectral analysis of fundus autofluorescence pattern as a tool to detect early stages of degeneration in the retina and retinal pigment epithelium. [Journal Article]
- EEye (Lond) 2018 May 22
- CONCLUSIONS: Because photooxidation and photodegradation products of bisretinoids are markers of photodestructive processes, which can cause RPE cell death and initiate degenerative processes in the retina, quantitative determination of increases in these bisretinoid products in lipofuscin granules may be used to establish quantitative diagnostic criteria for degenerative processes in the retina and RPE.
- Preventing the Growth of Geographic Atrophy: An Important Therapeutic Target in Age-Related Macular Degeneration. [Editorial]
- OOphthalmology 2018; 125(6):794-795
- A monoclonal antibody targeting amyloid β (Aβ) restores complement factor I bioactivity: Potential implications in age-related macular degeneration and Alzheimer's disease. [Journal Article]
- PlosPLoS One 2018; 13(5):e0195751
- Activation of the alternative complement cascade has been implicated in the pathogenesis of age related macular degeneration (AMD) and Alzheimer's disease (AD). Amyloid β (Aβ), a component of drusen,...
Activation of the alternative complement cascade has been implicated in the pathogenesis of age related macular degeneration (AMD) and Alzheimer's disease (AD). Amyloid β (Aβ), a component of drusen, may promote complement activation by inhibiting CFI bioactivity. We determined whether Aβ reduced CFI bioactivity and whether antibodies against Aβ including a monoclonal antibody, GSK933776 could restore CFI bioactivity. We also measured CFI bioactivity in plasma of subjects with AMD and AD. In support of the GSK933776 development program in AMD (geographic atrophy), we developed a quantitative assay to measure CFI bioactivity based on its ability to cleave C3b to iC3b, and repeated it in presence or absence of Aβ and anti-Aβ antibodies. Using this assay, we measured CFI bioactivity in plasma of 194 subjects with AMD, and in samples from subjects with AD that had been treated with GSK933776 as part of the GSK933776 development program in AD. Aβ reduced the CFI bioactivity by 5-fold and pre-incubation with GSK933776 restored CFI bioactivity. In subjects with AMD, plasma CFI levels and bioactivity were not significantly different from non-AMD controls. However, we detected a positive linear trend, suggesting increasing activity with disease severity. In subjects with AD, we observed a 10% and 27% increase in overall CFI bioactivity after treatment with GSK933776 during the second and third dose. Our studies indicate that CFI enzymatic activity can be inhibited by Aβ and be altered in proinflammatory diseases such as AMD and AD, in which deposition of Aβ and activation of the alternative complement cascade are believed to play a key role in the disease process.
New Search Next
- PROGNOSTIC VALUE OF SHAPE-DESCRIPTIVE FACTORS FOR THE PROGRESSION OF GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION. [Journal Article]
- RRetina 2018 May 16
- CONCLUSIONS: These findings confirm the relevance of shape-descriptive factors and previous progression as prognostic variables for geographic atrophy progression. However, a substantial part of the remaining variation in geographic atrophy progression seems to depend on other variables, some of which are visible in optical coherence tomography.