advertisement

---

1 General aspects (0)   1.1 Epidemiology (6)   1.2 Population genetics (0)   1.3 Pathogenesis (0)   1.4 Quality of life (12)   1.5 Glaucomas as cause of blindness (6)   1.6 Prevention and screening (15) 2 Anatomical structures in glaucoma (0)   2.1 Conjunctiva (3)   2.2 Cornea (18)   2.3 Sclera (3)   2.4 Anterior chamber angle (4)   2.5 Meshwork (0)     2.5.1 Trabecular meshwork (9)     2.5.2 Schlemms canal (2)     2.5.3 Scleral outlet channels (0)   2.6 Aqueous humor dynamics (1)     2.6.1 Production (0)     2.6.2 Outflow (0)       2.6.2.1 Trabecular meshwork (1)       2.6.2.2 Uveoscleral (0)     2.6.3 Compostion (5)   2.7 Episcleral veins and venous pressure (0)   2.8 Iris (6)   2.9 Ciliary body (0)   2.10 Lens (1)   2.11 Vitreous body (0)   2.12 Choroid, peripapillary choroid, peripapillary atrophy (1)   2.13 Retina and retinal nerve fibre layer (26)   2.14 Optic disc (21)   2.15 Optic nerve (2)   2.16 Chiasma and retrochiasmal central nervous system (4)   2.17 Stem cells (3)   2.20 Other (0) 3 Laboratory methods (0)   3.1 Microscopy (0)   3.2 Electron microscopy (0)   3.3 Immunohistochemistry (0)   3.4 Molecular genetics (0)     3.4.1 Linkage studies (0)     3.4.2 Gene studies (20)   3.5 Molecular biology incl. SiRNA (15)   3.6 Cellular biology (21)   3.7 Biochemistry (9)   3.8 Pharmacology (12)   3.9 Pathophysiology (17)   3.10 Immunobiology (8)   3.11 Pharmacogenetics (0)   3.12 Proteomics (3)   3.13 In vivo imaging (0)     3.13.1 Laser Scanning (0)       3.13.1.1 Confocal Scanning Laser Ophthalmoscopy (0)       3.13.1.2 Confocal Scanning Laser Polarimetry (0)     3.13.2 Optical Coherence Tomography (0)       3.13.2.1 Anterior Segment (0)       3.13.2.2 Posterior Segment (0)     3.13.3 RGC Imaging (2)     3.13.4 Other (0)   3.20 Other (0) 4 Tissue culture of ocular cells (0) 5 Experimental glaucoma; animal models (0)   5.1 Rodent (15)   5.2 Primates (0)   5.3 Other (1) 6 Clinical examination methods (0)   6.1 Intraocular pressure measurement; factors affecting IOP (0)     6.1.1 Devices, techniques (11)     6.1.2 Fluctuation, circadian rhythms (2)     6.1.3 Factors affecting IOP (8)   6.2 Tonography, aqueous flow measurement (see also 2.6) (0)   6.3 Biomicroscopy (slitlamp) (0)     6.3.1 Anterior segment (0)     6.3.2 Posterior segment (0)   6.4 Gonioscopy (5)   6.5 Ophthalmoscopy (0)   6.6 Visual field examination and other visual function tests (0)     6.6.1 Conventional manual (0)     6.6.2 Automated (28)     6.6.3 Special methods (e.g. color, contrast, SWAP etc.) (10)   6.7 Electro-ophthalmodiagnosis (8)   6.8 Photography (0)     6.8.1 Anterior segment (2)     6.8.2 Posterior segment (11)   6.9 Computerized image analysis (0)     6.9.1 Laser scanning (0)       6.9.1.1 Confocal Scanning Laser Ophthalmoscopy (3)       6.9.1.2 Confocal Scanning Laser Polarimetry (1)     6.9.2 Optical coherence tomography (0)       6.9.2.1 Anterior (13)       6.9.2.2 Posterior (56)     6.9.5 Other (16)   6.10 Fluorescein (ICG) angiography (0)     6.10.1 Anterior segment (0)     6.10.2 Posterior segment (0)   6.11 Bloodflow measurements (23)   6.12 Ultrasonography and ultrasound biomicroscopy (7)   6.13 Provocative tests (1)   6.19 Telemedicine (7)   6.20 Progression (11)   6.30 Other (5) 8 Refractive errors in relation to glaucoma (0)   8.1 Myopia (6)   8.2 Hypermetropia (0)   8.3 Contact lenses (0)   8.4 Refractive surgical procedures (1)   8.5 Other (0) 9 Clinical forms of glaucomas (0)   9.1 Developmental glaucomas (0)     9.1.1 Congenital glaucoma, Buphthalmos (15)     9.1.2 Juvenile glaucoma (15)     9.1.3 Syndromes of Axenfeld, Rieger, Peters, aniridia (1)     9.1.4 Other (0)   9.2 Primary open angle glaucomas (0)     9.2.1 Ocular hypertension (5)     9.2.2 Other risk factors for glaucoma (6)     9.2.3 Open angle glaucoma with elevated IOP (4)     9.2.4 Normal pressure glaucoma (9)   9.3 Primary angle closure glaucomas (0)     9.3.1 Acute primary angle closure glaucoma (pupillary block) (7)     9.3.2 Chronic primary angle closure glaucoma (pupillary block) (11)     9.3.3 Plateau iris syndrome (1)     9.3.4 Primary angle closure suspect (1)     9.3.5 Primary angle closure (2)     9.3.10 Other (0)   9.4 Glaucomas associated with other ocular and systemic disorders (0)     9.4.1 Steroid-induced glaucoma (7)     9.4.2 Glaucomas associated with disorders of the cornea, conjunctiva, sclera (0)       9.4.2.1 Iridocorneal endothelial syndrome (ICE, incl. irisatrophy) (1)       9.4.2.2 Posterior polymorphous dystrophy (0)       9.4.2.3 Fuchs' endothelial dystrophy (0)       9.4.2.5 Other (2)     9.4.3 Glaucomas associated with disorders of the iris and ciliary body (0)       9.4.3.1 Pigmentary glaucoma (1)       9.4.3.5 Other (1)     9.4.4 Glaucomas associated with disorders of the lens (0)       9.4.4.1 Exfoliation syndrome (7)       9.4.4.2 Glaucomas associated with cataracts (3)       9.4.4.3 Glaucomas associated with lens dislocation (0)       9.4.4.5 Other (0)     9.4.5 Glaucomas associated with disorders of the retina, choroid and vitreous (0)       9.4.5.1 Neovascular glaucoma (5)       9.4.5.5 Other (5)     9.4.6 Glaucomas associated with inflammation, uveitis (11)     9.4.7 Glaucomas associated with ocular trauma (2)     9.4.8 Glaucomas associated with intraocular tumors (0)     9.4.9 Glaucomas associated with elevated episcleral venous pressure (0)       9.4.10 Glaucomas associated with hemorrhage (4)     9.4.11 Glaucomas following intraocular surgery (0)       9.4.11.1 Ciliary block (malignant) glaucoma (1)       9.4.11.2 Glaucomas in aphakia and pseudophakia (6)       9.4.11.3 Epithelial, fibrous, and endothelial proliferation (0)       9.4.11.4 Glaucomas associated with corneal surgery (9)       9.4.11.5 Glaucomas associated with vitreoretinal surgery (0)     9.4.15 Glaucoma in relation to systemic disease (36)     9.4.20 Other (5) 10 Differential diagnosis e.g. anterior and posterior ischemic optic neuropathy (1) 11 Medical treatment (0)   11.1 General management, indication (3)   11.2 Cholinergic drugs (0)   11.3 Adrenergic drugs (0)     11.3.1 Epinephrine (0)     11.3.2 Thymoxamine, dapiprazole (0)     11.3.3 Apraclonidine, brimonidine (2)     11.3.4 Betablocker (0)     11.3.5 Other (0)   11.4 Prostaglandins (11)   11.5 Carbonic anhydrase inhibitors (0)     11.5.1 Systemic (1)     11.5.2 Topical (1)   11.6 Osmotic treatment (0)   11.7 Treatment of bloodflow (0)   11.8 Neuroprotection (17)   11.9 Gene therapy (2)   11.13 Combination therapy (0)     11.13.1 Betablocker and pilocarpine (0)     11.13.2 Betablocker and carbon anhydrase inhibitor (0)     11.13.3 Betablocker and brimonidine (0)     11.13.4 Betablocker and prostaglandin (1)     11.13.5 Other (1)   11.14 Investigational drugs; pharmacological experiments (4)   11.15 Other drugs in relation to glaucoma (10)   11.16 Vehicles, delivery systems, pharmacokinetics, formulation (12)   11.17 Cooperation with medical therapy e.g. persistency, compliance, adherence (11)   11.20 Other (0) 12 Surgical treatment (0)   12.1 General management, indication (7)   12.2 Laser iridotomy (3)   12.3 Laser iridoplasty (1)   12.4 Laser trabeculoplasty and other laser treatment of the angle (12)   12.7 Surgical iridectomy (2)   12.8 Filtering surgery (0)     12.8.1 Without tube implant (21)     12.8.2 With tube implant or other drainage devices (72)     12.8.3 Non-perforating (9)     12.8.4 Using laser (1)     12.8.5 Other (0)     12.8.10 Woundhealing antifibrosis (11)     12.8.11 Complications, endophthalmitis (16)   12.9 Trabeculotomy, goniotomy (25)   12.10 Cyclodestruction (9)   12.11 Cyclodialysis (0)   12.12 Cataract extraction (0)     12.12.1 Intracapsular (0)     12.12.2 Extracapsular (0)     12.12.3 Phacoemulsification (7)   12.14 Combined cataract extraction and glaucoma surgery (0)     12.14.1 Intracapsular (0)     12.14.2 Extracapsular (0)     12.14.3 Phacoemulsification (14)   12.15 Capsulotomy (0)   12.16 Vitrectomy (0)   12.17 Anesthesia (1)   12.20 Other (1) 13 Therapeutic prognosis and outcome (0)   13.1 Prognostic factors (3)   13.2 Outcome (0)     13.2.1 IOP (1)     13.2.2 Visual field (0)       13.2.2.1 Progression (0)       13.2.2.2 Improvement (1)     13.2.3 Other (0) 14 Costing studies; pharmacoeconomics (3) 15 Miscellaneous (47)

---

Abstract #95417 Published in IGR 22-2

Impaired cholesterol efflux in retinal pigment epithelium of individuals with juvenile macular degeneration

Tsai YT; Li Y; Ryu J; Su PY; Su PY; Cheng CH; Wu WH; Li YS; Quinn PMJ; Quinn PMJ; Quinn PMJ; Leong KW; Tsang SH
American Journal of Human Genetics 2021; 108: 903-918

---

Macular degeneration (MD) is characterized by the progressive deterioration of the macula and represents one of the most prevalent causes of blindness worldwide. Abnormal intracellular accumulation of lipid droplets and pericellular deposits of lipid-rich material in the retinal pigment epithelium (RPE) called drusen are clinical hallmarks of different forms of MD including Doyne honeycomb retinal dystrophy (DHRD) and age-related MD (AMD). However, the appropriate molecular therapeutic target underlying these disorder phenotypes remains elusive. Here, we address this knowledge gap by comparing the proteomic profiles of induced pluripotent stem cell (iPSC)-derived RPEs (iRPE) from individuals with DHRD and their isogenic controls. Our analysis and follow-up studies elucidated the mechanism of lipid accumulation in DHRD iRPE cells. Specifically, we detected significant downregulation of carboxylesterase 1 (CES1), an enzyme that converts cholesteryl ester to free cholesterol, an indispensable process in cholesterol export. CES1 knockdown or overexpression of EFEMP1, a variant of EGF-containing fibulin extracellular matrix protein 1 that is associated with DHRD and attenuated cholesterol efflux and led to lipid droplet accumulation. In iRPE cells, we also found that EFEMP1 has a hyper-inhibitory effect on epidermal growth factor receptor (EGFR) signaling when compared to EFEMP1 and may suppress CES1 expression via the downregulation of transcription factor SP1. Taken together, these results highlight the homeostatic role of cholesterol efflux in iRPE cells and identify CES1 as a mediator of cholesterol efflux in MD.

Department of Biomedical Engineering, Columbia University, New York, NY 10032, USA.

Full article

---

Classification:

---

• ← Previous
• Next →

---