Central insulin resistance, the diminished cellular sensitivity to insulin in the brain, has been implicated in diabetes mellitus, Alzheimer’s disease and other neurological disorders. However, whether and how centra...Central insulin resistance, the diminished cellular sensitivity to insulin in the brain, has been implicated in diabetes mellitus, Alzheimer’s disease and other neurological disorders. However, whether and how central insulin resistance plays a role in the eye remains unclear. Here, we performed intracerebroventricular injection of S961, a potent and specific blocker of insulin receptor in adult Wistar rats to test if central insulin resistance leads to pathological changes in ocular structures. 80 mg of S961 was stereotaxically injected into the lateral ventricle of the experimental group twice at 7 days apart, whereas buffer solution was injected to the sham control group. Blood samples, intraocular pressure, trabecular meshwork morphology, ciliary body markers, retinal and optic nerve integrity, and whole genome expression patterns were then evaluated. While neither blood glucose nor serum insulin level was significantly altered in the experimental or control group, we found that injection of S961 but not buffer solution significantly increased intraocular pressure at 14 and 24 days after first injection, along with reduced porosity and aquaporin 4 expression in the trabecular meshwork, and increased tumor necrosis factor α and aquaporin 4 expression in the ciliary body. In the retina, cell density and insulin receptor expression decreased in the retinal ganglion cell layer upon S961 injection. Fundus photography revealed peripapillary atrophy with vascular dysregulation in the experimental group. These retinal changes were accompanied by upregulation of pro-inflammatory and pro-apoptotic genes, downregulation of anti-inflammatory, anti-apoptotic, and neurotrophic genes, as well as dysregulation of genes involved in insulin signaling. Optic nerve histology indicated microglial activation and changes in the expression of glial fibrillary acidic protein, tumor necrosis factor α, and aquaporin 4. Molecular pathway architecture of the retina revealed the three most significant pathways involved being inflammation/cell stress, insulin signaling, and extracellular matrix regulation relevant to neurodegeneration. There was also a multimodal crosstalk between insulin signaling derangement and inflammation-related genes. Taken together, our results indicate that blocking insulin receptor signaling in the central nervous system can lead to trabecular meshwork and ciliary body dysfunction, intraocular pressure elevation, as well as inflammation, glial activation, and apoptosis in the retina and optic nerve. Given that central insulin resistance my lead to neurodegenerative phenotype in the visual system, targeting insulin signaling may hold promise for vision disorders involving the retina and optic nerve.展开更多
AIM： To evaluate ocular surface changes and its correlation with the central corneal subbasal nerve fibre layer in chronic glaucoma patients. METHODS： A prospective comparative study of ocular surface evaluation wa...AIM： To evaluate ocular surface changes and its correlation with the central corneal subbasal nerve fibre layer in chronic glaucoma patients. METHODS： A prospective comparative study of ocular surface evaluation was performed in 50 eyes of 25 patients using two or more antiglaucoma medications for at least 6too and 50 eyes of 25 normal subjects without any ocular problems as controls. The study parameters evaluated included visual acuity, intraocular pressure, ocular surface evaluation parameters [fluorescein break-up time （FTBUT）, Schirmer＇s I test, ocular surface staining scores and ocular surface disease index score （OSDI）], central corneal sensation （Cochet Bonnett aesthesiometer）, central subbasal nerve fiber layer density （SBNFLD） by confocal microscopy. RESULTS： The mean values in the glaucoma cases and control groups respectively were as follows： OSDI score （35.89±16.07/6.02±3.84; P=-0.001）, Schirmer＇s I test score （7.632.64 mm/12.86±1.93 mm; P=-0.001）, FTBUT （9.442.76s/11.8±1.88s; P=0.001）, corneal （5.7±2.33/ 1.1±0.58; P=0.001） and conjunctival staining score （5.061.94/0.84±0.46; P=0.001）, corneal sensitivity （4.68±0.44/5.07±0.37; P=0.076）, mean subbasal nerve fiber number （3.58±0.99/5.40±1.70; P=0.001）, SBNFL length （1101.44±287.56 pm/1963.70±562.56 pro; P=0.001） and density （6883.941798.03 pm/mm/12 273.153516.04 pm/mm2; P=O.O01）. Dry eye severity of level 2 and 3 was seen in 66% of glaucoma group. Corneal （/=0.86） and conjunctival staining （R2=0.71） and OSDI score （R=0.67） showed statistically significant negative correlation with central corneal SBNFLD while FTBUT （R==0.84）, corneal sensitivity （/=0.52） showed positive correlation to central corneal SBNFLD in the long term topical antiglaucoma medication group. CONCLUSION： Ocular surface changes and antiglaucoma therapy induced dry eye is found to be associated with decreased SBNFLD in eyes on long term topical antiglaucoma medications.展开更多
Noncontact slit lamp examination of the ocular fundus has been classically done using high power convex lenses like+90D,+78D,and+60D.A real and inverted image of the fundus is formed in between the high power convex l...Noncontact slit lamp examination of the ocular fundus has been classically done using high power convex lenses like+90D,+78D,and+60D.A real and inverted image of the fundus is formed in between the high power convex lens and the slit lamp.The+20D lens is commonly used for binocular indirect ophthalmoscopy.The authors use this+20D lens展开更多
Azuara-Blanco et al.(1)in their multicentric“EAGLE”study have done a remarkable work in comparing efficacy of clear lens extraction(CLE)vs.laser peripheral iridotomy(LPI)in 155 eyes having newly diagnosed primary an...Azuara-Blanco et al.(1)in their multicentric“EAGLE”study have done a remarkable work in comparing efficacy of clear lens extraction(CLE)vs.laser peripheral iridotomy(LPI)in 155 eyes having newly diagnosed primary angle closure(PAC)with ocular hypertension(IOP≥30 mmHg)and 263 eyes with early to moderate primary angle closure glaucoma(PACG).The authors reported better quality of life scores and a mean intraocular pressure lower by 1 mmHg in eyes which underwent CLE as compared to LPI at 36 months follow-up.The conclusion of the study was that CLE has a greater efficacy and is more cost effective as compared to the current standard of care(LPI followed by topical therapy)and should therefore be considered as the first line therapy in management of PAC disease(PAC and PACG).展开更多
基金supported by a grant from All India Institute of Medical Sciences,New Delhi (to RD and TD)Indian Council of Medical Research,Senior Research Fellowship Grant (3/1/2(24)/oph-2009-NCD-II,to MAF)+1 种基金Feldstein Medical Foundation Research Grant (to KCC)unrestricted fund from Research to Prevent Blindness to NYU Langone Health Department of Ophthalmology (to KCC)。
文摘Central insulin resistance, the diminished cellular sensitivity to insulin in the brain, has been implicated in diabetes mellitus, Alzheimer’s disease and other neurological disorders. However, whether and how central insulin resistance plays a role in the eye remains unclear. Here, we performed intracerebroventricular injection of S961, a potent and specific blocker of insulin receptor in adult Wistar rats to test if central insulin resistance leads to pathological changes in ocular structures. 80 mg of S961 was stereotaxically injected into the lateral ventricle of the experimental group twice at 7 days apart, whereas buffer solution was injected to the sham control group. Blood samples, intraocular pressure, trabecular meshwork morphology, ciliary body markers, retinal and optic nerve integrity, and whole genome expression patterns were then evaluated. While neither blood glucose nor serum insulin level was significantly altered in the experimental or control group, we found that injection of S961 but not buffer solution significantly increased intraocular pressure at 14 and 24 days after first injection, along with reduced porosity and aquaporin 4 expression in the trabecular meshwork, and increased tumor necrosis factor α and aquaporin 4 expression in the ciliary body. In the retina, cell density and insulin receptor expression decreased in the retinal ganglion cell layer upon S961 injection. Fundus photography revealed peripapillary atrophy with vascular dysregulation in the experimental group. These retinal changes were accompanied by upregulation of pro-inflammatory and pro-apoptotic genes, downregulation of anti-inflammatory, anti-apoptotic, and neurotrophic genes, as well as dysregulation of genes involved in insulin signaling. Optic nerve histology indicated microglial activation and changes in the expression of glial fibrillary acidic protein, tumor necrosis factor α, and aquaporin 4. Molecular pathway architecture of the retina revealed the three most significant pathways involved being inflammation/cell stress, insulin signaling, and extracellular matrix regulation relevant to neurodegeneration. There was also a multimodal crosstalk between insulin signaling derangement and inflammation-related genes. Taken together, our results indicate that blocking insulin receptor signaling in the central nervous system can lead to trabecular meshwork and ciliary body dysfunction, intraocular pressure elevation, as well as inflammation, glial activation, and apoptosis in the retina and optic nerve. Given that central insulin resistance my lead to neurodegenerative phenotype in the visual system, targeting insulin signaling may hold promise for vision disorders involving the retina and optic nerve.
基金Supported by the Institute Research Grant of All India Institute of Medical Sciences,New Delhi 110029,India
文摘AIM： To evaluate ocular surface changes and its correlation with the central corneal subbasal nerve fibre layer in chronic glaucoma patients. METHODS： A prospective comparative study of ocular surface evaluation was performed in 50 eyes of 25 patients using two or more antiglaucoma medications for at least 6too and 50 eyes of 25 normal subjects without any ocular problems as controls. The study parameters evaluated included visual acuity, intraocular pressure, ocular surface evaluation parameters [fluorescein break-up time （FTBUT）, Schirmer＇s I test, ocular surface staining scores and ocular surface disease index score （OSDI）], central corneal sensation （Cochet Bonnett aesthesiometer）, central subbasal nerve fiber layer density （SBNFLD） by confocal microscopy. RESULTS： The mean values in the glaucoma cases and control groups respectively were as follows： OSDI score （35.89±16.07/6.02±3.84; P=-0.001）, Schirmer＇s I test score （7.632.64 mm/12.86±1.93 mm; P=-0.001）, FTBUT （9.442.76s/11.8±1.88s; P=0.001）, corneal （5.7±2.33/ 1.1±0.58; P=0.001） and conjunctival staining score （5.061.94/0.84±0.46; P=0.001）, corneal sensitivity （4.68±0.44/5.07±0.37; P=0.076）, mean subbasal nerve fiber number （3.58±0.99/5.40±1.70; P=0.001）, SBNFL length （1101.44±287.56 pm/1963.70±562.56 pro; P=0.001） and density （6883.941798.03 pm/mm/12 273.153516.04 pm/mm2; P=O.O01）. Dry eye severity of level 2 and 3 was seen in 66% of glaucoma group. Corneal （/=0.86） and conjunctival staining （R2=0.71） and OSDI score （R=0.67） showed statistically significant negative correlation with central corneal SBNFLD while FTBUT （R==0.84）, corneal sensitivity （/=0.52） showed positive correlation to central corneal SBNFLD in the long term topical antiglaucoma medication group. CONCLUSION： Ocular surface changes and antiglaucoma therapy induced dry eye is found to be associated with decreased SBNFLD in eyes on long term topical antiglaucoma medications.
文摘Noncontact slit lamp examination of the ocular fundus has been classically done using high power convex lenses like+90D,+78D,and+60D.A real and inverted image of the fundus is formed in between the high power convex lens and the slit lamp.The+20D lens is commonly used for binocular indirect ophthalmoscopy.The authors use this+20D lens
文摘Azuara-Blanco et al.(1)in their multicentric“EAGLE”study have done a remarkable work in comparing efficacy of clear lens extraction(CLE)vs.laser peripheral iridotomy(LPI)in 155 eyes having newly diagnosed primary angle closure(PAC)with ocular hypertension(IOP≥30 mmHg)and 263 eyes with early to moderate primary angle closure glaucoma(PACG).The authors reported better quality of life scores and a mean intraocular pressure lower by 1 mmHg in eyes which underwent CLE as compared to LPI at 36 months follow-up.The conclusion of the study was that CLE has a greater efficacy and is more cost effective as compared to the current standard of care(LPI followed by topical therapy)and should therefore be considered as the first line therapy in management of PAC disease(PAC and PACG).
