- Keeping an Eye on Bardet-Biedl Syndrome: A Comprehensive Review of the Role of Bardet-Biedl Syndrome Genes in the Eye. [Journal Article]
- MRMed Res Arch 2017; 5(9)
- Upwards of 90% of individuals with Bardet-Biedl syndrome (BBS) display rod-cone dystrophy with early macular involvement. BBS is an autosomal recessive, genetically heterogeneous, pleiotropic ciliopa...
Upwards of 90% of individuals with Bardet-Biedl syndrome (BBS) display rod-cone dystrophy with early macular involvement. BBS is an autosomal recessive, genetically heterogeneous, pleiotropic ciliopathy for which 21 causative genes have been discovered to date. In addition to retinal degeneration, the cardinal features of BBS include obesity, cognitive impairment, renal anomalies, polydactyly, and hypogonadism. Here, we review the genes, proteins, and protein complexes involved in BBS and the BBS model organisms available for the study of retinal degeneration. We include comprehensive lists for all known BBS genes, their known phenotypes, and the model organisms available. We also review the molecular mechanisms believed to lead to retinal degeneration. We provide an overview of the mode of inheritance and describe the relationships between BBS genes and Joubert syndrome, Leber Congenital Amaurosis, Senior-Løken syndrome, and non-syndromic retinitis pigmentosa. Finally, we propose ways that new advances in technology will allow us to better understand the role of different BBS genes in retinal formation and function.
- Distinct CD40L receptors mediate inflammasome activation and secretion of IL-1β and MCP-1 in cultured human retinal pigment epithelial cells. [Journal Article]
- EEExp Eye Res 2018 Feb 15
- CD40L signaling occurs in several diseases with inflammatory components, including ocular and retinal diseases. However, it has never been evaluated as a pathogenic mechanism in age-related macular d...
CD40L signaling occurs in several diseases with inflammatory components, including ocular and retinal diseases. However, it has never been evaluated as a pathogenic mechanism in age-related macular degeneration (AMD) or as an inducer of inflammasome formation in any cell type. mRNA and protein levels of CD40, IL-1β, NALP1, NALP3, caspase-1, and caspase-5 were determined by RT-PCR, qPCR, and Western blot. CD40L receptor (CD40, α5β1, and CD11b) expression was determined by Western and immunofluorescent staining. IL-1β, IL-18, and MCP-1 secretions were determined by ELISA. NALP1 and NALP3 inflammasome formation were determined by Co-IP. Experiments were conducted on primary human retinal pigment epithelial (hRPE) cells from four different donors. Human umbilical vein endothelial (HUVEC) and monocytic leukemia (THP-1) cells demonstrated the general applicability of our findings. In hRPE cells, CD40L-induced NALP1 and NALP3 inflammasome activation, cleavage of caspase-1 and caspase-5, and IL-1β and IL-18 secretion. Interestingly, neutralizing CD11b and α5β1 antibodies, but not CD40, reduced CD40L-induced IL-1β secretion in hRPE cells. Similarly, CD40L treatment also induced HUVEC and THP-1 cells to secret IL-1β through CD11b and α5β1. Additionally, the CD40L-induced IL-1β secretion acted in an autocrine/paracrine manner to feed back and induce hRPE cells to secrete MCP-1. This study is the first to show that CD40L induces inflammasome activation in any cell type, including hRPE cells, and that this induction is through CD11b and α5β1 cell-surface receptors. These mechanisms likely play an important role in many retinal and non-retinal diseases and provide compelling drug targets that may help reduce pro-inflammatory processes.
- Development and Course of Scars in the Comparison of Age-related Macular Degeneration Treatments Trials. [Journal Article]
- OOphthalmology 2018 Feb 14
- CONCLUSIONS: Several morphologic features, including classic CNV and large hemorrhage, are associated with scar formation. Rate of new scar formation declined after 2 years. Most fibrotic scars and accompanying macular atrophy expanded over time, reducing VA.
- Predicting Visual Acuity by Using Machine Learning in Patients Treated for Neovascular Age-Related Macular Degeneration. [Journal Article]
- OOphthalmology 2018 Feb 14
- CONCLUSIONS: Machine learning allowed VA to be predicted for 3 months with a comparable result to VA measurement reliability. For a forecast after 12 months of therapy, VA prediction may help to encourage patients adhering to intravitreal therapy.
- Prevalence of age-related macular degeneration associated genetic risk factors and 4-year progression data in the Irish population. [Journal Article]
- BJBr J Ophthalmol 2018 Feb 16
- CONCLUSIONS: The prevalence of risk-associated genes and 4-year progression rates of AMD in this Ireland cohort are comparable with other Caucasian populations. CFH Y402H is associated with disease progression, with soft drusen and hyperpigmentation as high-risk features.
- Tissue engineering of retina and Bruch's membrane: a review of cells, materials and processes. [Review]
- BJBr J Ophthalmol 2018 Feb 16
- The biological, structural and functional configuration of Bruch's membrane (BM) is significantly relevant to age-related macular degeneration (AMD) and other chorioretinal diseases, and AMD is one o...
The biological, structural and functional configuration of Bruch's membrane (BM) is significantly relevant to age-related macular degeneration (AMD) and other chorioretinal diseases, and AMD is one of the leading causes of blindness in the elderly worldwide. The configuration may worsen along with the ageing of retinal pigment epithelium and BM that finally leads to AMD. Thus, the scaffold-based tissue-engineered retina provides an innovative alternative for retinal tissue repair. The cell and material requirements for retinal repair are discussed including cell sheet engineering, decellularised membrane and tissue-engineered membranes. Further, the challenges and potential in realising a whole tissue model construct for retinal regeneration are highlighted herein. This review article provides a framework for future development of tissue-engineered retina as a preclinical model and possible treatments for AMD.
- Intravitreal Aflibercept Versus Ranibizumab for Wet Age-Related Macular Degeneration: A Cost-effectiveness Analysis. [Journal Article]
- JMJ Manag Care Spec Pharm 2018 Feb 16; :1-9
- CONCLUSIONS: IAI 2q8 can be cost saving and cost-effective compared with Rq4 and ranibizumab PRN for the treatment of wAMD in the United States.
- Induction of Ocular Complement Activation by Inflammatory Stimuli and Intraocular Inhibition of Complement Factor D in Animal Models. [Journal Article]
- IOInvest Ophthalmol Vis Sci 2018 Feb 01; 59(2):940-951
- CONCLUSIONS: Systemic TLR stimulation and eye tissue injury induced time-dependent alternative complement pathway activation in the eye. Ocular complement levels were also gradually elevated during aging. An anti-FD antibody IVT potently inhibited LPS-induced complement activation in the posterior segment of the eye. This study provides insights into the dynamic profile of ocular complement activation, which is valuable for complement research in eye diseases and for developing complement therapeutics for AMD.
- Incidence of ocular hypertension after intravitreal injection of anti-VEGF agents in the treatment of neovascular AMD. [Journal Article]
- RJRom J Ophthalmol 2017 Jul-Sep; 61(3):207-211
- Purpose. The assessment of the incidence of ocular hypertension over a period of 1 year in patients treated with multiple intravitreal injections of anti-VEGF agents for neovascul...
Purpose. The assessment of the incidence of ocular hypertension over a period of 1 year in patients treated with multiple intravitreal injections of anti-VEGF agents for neovascular AMD.Methods.The study comprised 58 eyes diagnosed with neovascular age-related macular degeneration and receiving PRN intravitreal treatment with anti-VEGF agents (bevacizumab or aflibercept). The follow-up period was 1 year. Intraocular pressure was measured by using the Goldmann applanation tonometry before the intravitreal injection, at 24 hours after the administration of the anti-VEGF agent and at 1 and 4 weeks. Patients diagnosed with glaucoma or who underwent ophthalmic surgery were excluded.Results.The patients received an average of 7.54 intravitreal injections. The mean baseline intraocular pressure was 15.3 mm Hg; 19.8 mm Hg at 24 hours; 17,4 mmHg at 1 week and 14.8 mmHg at 4 weeks after the administration of the anti-VEGF agent. 4 patients required long-term topical hypotensive treatment. Raised intraocular pressure was related to increased frequency of treatment. At 1 year follow up, an average difference of 2.1 mmHg compared to baseline was registered in the cases that have received more than 6 intravitreal injections. By comparison, in the cases treated with a reduced number of doses of intravitreal anti VEGF agent, the difference from baseline was 0,9 mmHg. There were no significant differences in mean IOP depending on the anti VEGF (bevacizumab or aflibercept) agent used.Conclusions.Intravitreal treatment with anti VEGF agents produces a transient increase in intraocular pressure, predominantly immediately following administration, without causing long-term increased values.
New Search Next
- Analysis combining correlated glaucoma traits identifies five new risk loci for open-angle glaucoma. [Journal Article]
- SRSci Rep 2018 Feb 15; 8(1):3124
- Open-angle glaucoma (OAG) is a major cause of blindness worldwide. To identify new risk loci for OAG, we performed a genome-wide association study in 3,071 OAG cases and 6,750 unscreened controls, an...
Open-angle glaucoma (OAG) is a major cause of blindness worldwide. To identify new risk loci for OAG, we performed a genome-wide association study in 3,071 OAG cases and 6,750 unscreened controls, and meta-analysed the results with GWAS data for intraocular pressure (IOP) and optic disc parameters (the overall meta-analysis sample size varying between 32,000 to 48,000 participants), which are glaucoma-related traits. We identified and independently validated four novel genome-wide significant associations within or near MYOF and CYP26A1, LINC02052 and CRYGS, LMX1B, and LMO7 using single variant tests, one additional locus (C9) using gene-based tests, and two genetic pathways - "response to fluid shear stress" and "abnormal retina morphology" - in pathway-based tests. Interestingly, some of the new risk loci contribute to risk of other genetically-correlated eye diseases including myopia and age-related macular degeneration. To our knowledge, this study is the first integrative study to combine genetic data from OAG and its correlated traits to identify new risk variants and genetic pathways, highlighting the future potential of combining genetic data from genetically-correlated eye traits for the purpose of gene discovery and mapping.