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1 General aspects (0)   1.1 Epidemiology (6)   1.2 Population genetics (0)   1.3 Pathogenesis (0)   1.4 Quality of life (13)   1.5 Glaucomas as cause of blindness (5)   1.6 Prevention and screening (3) 2 Anatomical structures in glaucoma (0)   2.1 Conjunctiva (5)   2.2 Cornea (19)   2.3 Sclera (11)   2.4 Anterior chamber angle (3)   2.5 Meshwork (0)     2.5.1 Trabecular meshwork (10)     2.5.2 Schlemms canal (1)     2.5.3 Scleral outlet channels (0)   2.6 Aqueous humor dynamics (0)     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 (6)   2.7 Episcleral veins and venous pressure (0)   2.8 Iris (6)   2.9 Ciliary body (0)   2.10 Lens (0)   2.11 Vitreous body (1)   2.12 Choroid, peripapillary choroid, peripapillary atrophy (15)   2.13 Retina and retinal nerve fibre layer (17)   2.14 Optic disc (28)   2.15 Optic nerve (0)   2.16 Chiasma and retrochiasmal central nervous system (5)   2.17 Stem cells (4)   2.20 Other (0) 3 Laboratory methods (0)   3.1 Microscopy (0)   3.2 Electron microscopy (0)   3.3 Immunohistochemistry (2)   3.4 Molecular genetics (0)     3.4.1 Linkage studies (0)     3.4.2 Gene studies (18)   3.5 Molecular biology incl. SiRNA (20)   3.6 Cellular biology (42)   3.7 Biochemistry (14)   3.8 Pharmacology (25)   3.9 Pathophysiology (26)   3.10 Immunobiology (10)   3.11 Pharmacogenetics (0)   3.12 Proteomics (1)   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 (0)     3.13.4 Other (1)   3.20 Other (0) 4 Tissue culture of ocular cells (0) 5 Experimental glaucoma; animal models (1)   5.1 Rodent (28)   5.2 Primates (0)   5.3 Other (8) 6 Clinical examination methods (1)   6.1 Intraocular pressure measurement; factors affecting IOP (1)     6.1.1 Devices, techniques (18)     6.1.2 Fluctuation, circadian rhythms (16)     6.1.3 Factors affecting IOP (9)   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 (0)   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 (29)     6.6.3 Special methods (e.g. color, contrast, SWAP etc.) (9)   6.7 Electro-ophthalmodiagnosis (11)   6.8 Photography (0)     6.8.1 Anterior segment (3)     6.8.2 Posterior segment (6)   6.9 Computerized image analysis (0)     6.9.1 Laser scanning (0)       6.9.1.1 Confocal Scanning Laser Ophthalmoscopy (0)       6.9.1.2 Confocal Scanning Laser Polarimetry (0)     6.9.2 Optical coherence tomography (0)       6.9.2.1 Anterior (5)       6.9.2.2 Posterior (47)     6.9.5 Other (11)   6.10 Fluorescein (ICG) angiography (0)     6.10.1 Anterior segment (0)     6.10.2 Posterior segment (0)   6.11 Bloodflow measurements (39)   6.12 Ultrasonography and ultrasound biomicroscopy (5)   6.13 Provocative tests (2)   6.19 Telemedicine (1)   6.20 Progression (17)   6.30 Other (11) 8 Refractive errors in relation to glaucoma (0)   8.1 Myopia (4)   8.2 Hypermetropia (0)   8.3 Contact lenses (5)   8.4 Refractive surgical procedures (0)   8.5 Other (0) 9 Clinical forms of glaucomas (0)   9.1 Developmental glaucomas (0)     9.1.1 Congenital glaucoma, Buphthalmos (9)     9.1.2 Juvenile glaucoma (17)     9.1.3 Syndromes of Axenfeld, Rieger, Peters, aniridia (3)     9.1.4 Other (1)   9.2 Primary open angle glaucomas (0)     9.2.1 Ocular hypertension (6)     9.2.2 Other risk factors for glaucoma (6)     9.2.3 Open angle glaucoma with elevated IOP (2)     9.2.4 Normal pressure glaucoma (14)   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) (4)     9.3.3 Plateau iris syndrome (0)     9.3.4 Primary angle closure suspect (1)     9.3.5 Primary angle closure (2)     9.3.10 Other (1)   9.4 Glaucomas associated with other ocular and systemic disorders (0)     9.4.1 Steroid-induced glaucoma (2)     9.4.2 Glaucomas associated with disorders of the cornea, conjunctiva, sclera (1)       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 (1)     9.4.3 Glaucomas associated with disorders of the iris and ciliary body (0)       9.4.3.1 Pigmentary glaucoma (2)       9.4.3.5 Other (0)     9.4.4 Glaucomas associated with disorders of the lens (0)       9.4.4.1 Exfoliation syndrome (22)       9.4.4.2 Glaucomas associated with cataracts (1)       9.4.4.3 Glaucomas associated with lens dislocation (1)       9.4.4.5 Other (1)     9.4.5 Glaucomas associated with disorders of the retina, choroid and vitreous (0)       9.4.5.1 Neovascular glaucoma (9)       9.4.5.5 Other (7)     9.4.6 Glaucomas associated with inflammation, uveitis (7)     9.4.7 Glaucomas associated with ocular trauma (2)     9.4.8 Glaucomas associated with intraocular tumors (5)     9.4.9 Glaucomas associated with elevated episcleral venous pressure (0)       9.4.10 Glaucomas associated with hemorrhage (6)     9.4.11 Glaucomas following intraocular surgery (3)       9.4.11.1 Ciliary block (malignant) glaucoma (2)       9.4.11.2 Glaucomas in aphakia and pseudophakia (9)       9.4.11.3 Epithelial, fibrous, and endothelial proliferation (0)       9.4.11.4 Glaucomas associated with corneal surgery (3)       9.4.11.5 Glaucomas associated with vitreoretinal surgery (4)     9.4.15 Glaucoma in relation to systemic disease (39)     9.4.20 Other (2) 10 Differential diagnosis e.g. anterior and posterior ischemic optic neuropathy (2) 11 Medical treatment (1)   11.1 General management, indication (2)   11.2 Cholinergic drugs (3)   11.3 Adrenergic drugs (1)     11.3.1 Epinephrine (0)     11.3.2 Thymoxamine, dapiprazole (0)     11.3.3 Apraclonidine, brimonidine (5)     11.3.4 Betablocker (7)     11.3.5 Other (0)   11.4 Prostaglandins (13)   11.5 Carbonic anhydrase inhibitors (0)     11.5.1 Systemic (2)     11.5.2 Topical (3)   11.6 Osmotic treatment (1)   11.7 Treatment of bloodflow (0)   11.8 Neuroprotection (34)   11.9 Gene therapy (1)   11.13 Combination therapy (2)     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 (2)     11.13.5 Other (2)   11.14 Investigational drugs; pharmacological experiments (2)   11.15 Other drugs in relation to glaucoma (7)   11.16 Vehicles, delivery systems, pharmacokinetics, formulation (19)   11.17 Cooperation with medical therapy e.g. persistency, compliance, adherence (11)   11.20 Other (1) 12 Surgical treatment (1)   12.1 General management, indication (0)   12.2 Laser iridotomy (0)   12.3 Laser iridoplasty (0)   12.4 Laser trabeculoplasty and other laser treatment of the angle (6)   12.7 Surgical iridectomy (2)   12.8 Filtering surgery (1)     12.8.1 Without tube implant (15)     12.8.2 With tube implant or other drainage devices (46)     12.8.3 Non-perforating (4)     12.8.4 Using laser (1)     12.8.5 Other (1)     12.8.10 Woundhealing antifibrosis (12)     12.8.11 Complications, endophthalmitis (11)   12.9 Trabeculotomy, goniotomy (8)   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 (8)   12.14 Combined cataract extraction and glaucoma surgery (0)     12.14.1 Intracapsular (0)     12.14.2 Extracapsular (0)     12.14.3 Phacoemulsification (4)   12.15 Capsulotomy (0)   12.16 Vitrectomy (4)   12.17 Anesthesia (1)   12.20 Other (2) 13 Therapeutic prognosis and outcome (0)   13.1 Prognostic factors (0)   13.2 Outcome (0)     13.2.1 IOP (0)     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 (6) 15 Miscellaneous (28)

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Abstract #86863 Published in IGR 21-2

Reprogramming to recover youthful epigenetic information and restore vision

Lu Y; Brommer B; Tian X; Krishnan A; Meer M; Wang C; Vera DL; Zeng Q; Yu D; Bonkowski MS; Yang JH; Zhou S; Hoffmann EM; Karg MM; Schultz MB; Kane AE; Davidsohn N; Korobkina E; Chwalek K; Rajman LA; Church GM; Hochedlinger K; Gladyshev VN; Horvath S; Levine ME; Gregory-Ksander MS; Ksander BR; He Z; Sinclair DA
Nature 2020; 588: 124-129

See also comment(s) by Keith Martin • Harry Quigley • Dorota Skowronska-Krawczyk • Derek Welsbie •

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Ageing is a degenerative process that leads to tissue dysfunction and death. A proposed cause of ageing is the accumulation of epigenetic noise that disrupts gene expression patterns, leading to decreases in tissue function and regenerative capacity1-3. Changes to DNA methylation patterns over time form the basis of ageing clocks4, but whether older individuals retain the information needed to restore these patterns-and, if so, whether this could improve tissue function-is not known. Over time, the central nervous system (CNS) loses function and regenerative capacity5-7. Using the eye as a model CNS tissue, here we show that ectopic expression of Oct4 (also known as Pou5f1), Sox2 and Klf4 genes (OSK) in mouse retinal ganglion cells restores youthful DNA methylation patterns and transcriptomes, promotes axon regeneration after injury, and reverses vision loss in a mouse model of glaucoma and in aged mice. The beneficial effects of OSK-induced reprogramming in axon regeneration and vision require the DNA demethylases TET1 and TET2. These data indicate that mammalian tissues retain a record of youthful epigenetic information-encoded in part by DNA methylation-that can be accessed to improve tissue function and promote regeneration in vivo.

Department of Genetics, Blavatnik Institute, Paul F. Glenn Center for Biology of Aging Research, Harvard Medical School, Boston, MA, USA.

Full article

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Classification:

3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)
3.6 Cellular biology (Part of: 3 Laboratory methods)
11.8 Neuroprotection (Part of: 11 Medical treatment)

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