In vivo imaging of structural,metabolic and functional brain changes in glaucoma
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摘要
Glaucoma, the world's leading cause of irreversible blindness, is a condition for which elevated intraocular pressure is currently the only modifiable risk factor. However, the disorder can continue to progress even at reduced intraocular pressure. This indicates additional key factors that contribute to the etiopathogenesis. There has been a growing amount of literature suggesting glaucoma as a neurodegenerative disease of the visual system. However, it remains debatable whether the observed pathophysiological conditions are causes or consequences. This review summarizes recent in vivo imaging studies that helped advance the understanding of early glaucoma involvements and disease progression in the brains of humans and experimental animal models. In particular, we focused on the non-invasive detection of early structural and functional brain changes before substantial clinical visual field loss in glaucoma patients; the eye-brain interactions across disease severity; the metabolic changes occurring in the brain's visual system in glaucoma; and, the widespread brain involvements beyond the visual pathway as well as the potential behavioral relevance. If the mechanisms of glaucomatous brain changes are reliably identified, novel neurotherapeutics that target parameters beyond intraocular pressure lowering can be the promise of the near future, which would lead to reduced prevalence of this irreversible but preventable disease.
Glaucoma, the world's leading cause of irreversible blindness, is a condition for which elevated intraocular pressure is currently the only modifiable risk factor. However, the disorder can continue to progress even at reduced intraocular pressure. This indicates additional key factors that contribute to the etiopathogenesis. There has been a growing amount of literature suggesting glaucoma as a neurodegenerative disease of the visual system. However, it remains debatable whether the observed pathophysiological conditions are causes or consequences. This review summarizes recent in vivo imaging studies that helped advance the understanding of early glaucoma involvements and disease progression in the brains of humans and experimental animal models. In particular, we focused on the non-invasive detection of early structural and functional brain changes before substantial clinical visual field loss in glaucoma patients; the eye-brain interactions across disease severity; the metabolic changes occurring in the brain's visual system in glaucoma; and, the widespread brain involvements beyond the visual pathway as well as the potential behavioral relevance. If the mechanisms of glaucomatous brain changes are reliably identified, novel neurotherapeutics that target parameters beyond intraocular pressure lowering can be the promise of the near future, which would lead to reduced prevalence of this irreversible but preventable disease.
Glaucoma, the world's leading cause of irreversible blindness, is a condition for which elevated intraocular pressure is currently the only modifiable risk factor. However, the disorder can continue to progress even at reduced intraocular pressure. This indicates additional key factors that contribute to the etiopathogenesis. There has been a growing amount of literature suggesting glaucoma as a neurodegenerative disease of the visual system. However, it remains debatable whether the observed pathophysiological conditions are causes or consequences. This review summarizes recent in vivo imaging studies that helped advance the understanding of early glaucoma involvements and disease progression in the brains of humans and experimental animal models. In particular, we focused on the non-invasive detection of early structural and functional brain changes before substantial clinical visual field loss in glaucoma patients; the eye-brain interactions across disease severity; the metabolic changes occurring in the brain's visual system in glaucoma; and, the widespread brain involvements beyond the visual pathway as well as the potential behavioral relevance. If the mechanisms of glaucomatous brain changes are reliably identified, novel neurotherapeutics that target parameters beyond intraocular pressure lowering can be the promise of the near future, which would lead to reduced prevalence of this irreversible but preventable disease.
引文
Cham R,O’Connell C,Redfern M,Conner IP,Wollstein G,Chan KC(2018)Balance and brain connectivity in glaucoma.Invest Ophthalmol Vis Sci59:1944.
Chan KC,So KF,Wu EX(2009)Proton magnetic resonance spectroscopy revealed choline reduction in the visual cortex in an experimental model of chronic glaucoma.Exp Eye Res 88:65-70.
Faiq MA,Dada T(2017)Diabetes type 4:a paradigm shift in the understanding of glaucoma,the brain specific diabetes and the candidature of insulin as a therapeutic agent.Curr Mol Med 17:46-59.
Frezzotti P,Giorgio A,Toto F,De Leucio A,De Stefano N(2016)Early changes of brain connectivity in primary open angle glaucoma.Hum Brain Mapp 37:4581-4596.
Gupta N,Ang LC,Noel de Tilly L,Bidaisee L,Yucel YH(2006)Human glaucoma and neural degeneration in intracranial optic nerve,lateral geniculate nucleus,and visual cortex.Br J Ophthalmol 90:674-678.
Lawlor M,Danesh-Meyer H,Levin LA,Davagnanam I,De Vita E,Plant GT(2018)Glaucoma and the brain:Trans-synaptic degeneration,structural change,and implications for neuroprotection.Surv Ophthalmol 63:296-306.
Murai H,Suzuki Y,Kiyosawa M,Tokumaru AM,Ishiwata K,Ishii K(2015)Cerebral glucose metabolism in the striate cortex positively correlates with fractional anisotropy values of the optic radiation in patients with glaucoma.Clin Exp Ophthalmol 43:711-719.
Murphy MC,Conner IP,Teng CY,Lawrence JD,Safiullah Z,Wang B,Bilonick RA,Kim SG,Wollstein G,Schuman JS,Chan KC(2016)Retinal structures and visual cortex activity are impaired prior to clinical vision loss in glaucoma.Sci Rep 6:31464.
Nuzzi R,Dallorto L,Rolle T(2018)Changes of visual pathway and brain connectivity in glaucoma:a systematic review.Front Neurosci 12:363.
Shimazawa M,Ito Y,Inokuchi Y,Yamanaka H,Nakanishi T,Hayashi T,Ji B,Higuchi M,Suhara T,Imamura K,Araie M,Watanabe Y,Onoe H,Hara H(2012)An alteration in the lateral geniculate nucleus of experimental glaucoma monkeys:in vivo positron emission tomography imaging of glial activation.PLoS One 7:e30526.
Sponsel WE,Groth SL,Satsangi N,Maddess T,Reilly MA(2014)Refined data analysis provides clinical evidence for central nervous system control of chronic glaucomatous neurodegeneration.Transl Vis Sci Technol 3:1.
Susanna R Jr,De Moraes CG,Cioffi GA,Ritch R(2015)Why Do People(Still)Go blind from glaucoma?Transl Vis Sci Technol 4:1.
Tham YC,Li X,Wong TY,Quigley HA,Aung T,Cheng CY(2014)Global prevalence of glaucoma and projections of glaucoma burden through2040:a systematic review and meta-analysis.Ophthalmology 121:2081-2090.
Trivedi V,Chen Y,Parra C,Arshad A,Bang JW,Wu M,Conner IP,Wollstein G,Schuman JS,Chan KC(2018)Evaluation of volumetric and diffusional brain changes and their associations with retinal structures and visual field function in glaucoma using MRI,OCT and perimetry.Invest Ophthalmol Vis Sci 59:3502.
van der Merwe Y,Yang X,Ho LC,Yu Y,Chau Y,Leung CK,Conner IP,Wollstein G,Schuman JS,Chan KC(2016)Citicoline preserves optic nerve integrity and visuomotor function following chronic intraocular pressure elevation.Invest Ophthalmol Vis Sci 57:3788-3800.
Wang R,Tang Z,Sun X,Wu L,Wang J,Zhong Y,Xiao Z(2018)White matter abnormalities and correlation with severity in normal tension glaucoma:a whole brain atlas-based diffusion tensor study.Invest Ophthalmol Vis Sci 59:1313-1322.
Yang XL,van der Merwe Y,Sims J,Parra C,Ho LC,Schuman JS,Wollstein G,Lathrop KL,Chan KC(2018)Age-related changes in eye,brain and visuomotor behavior in the DBA/2J mouse model of chronic glaucoma.Sci Rep8:4643.
Chan KC,So KF,Wu EX(2009)Proton magnetic resonance spectroscopy revealed choline reduction in the visual cortex in an experimental model of chronic glaucoma.Exp Eye Res 88:65-70.
Faiq MA,Dada T(2017)Diabetes type 4:a paradigm shift in the understanding of glaucoma,the brain specific diabetes and the candidature of insulin as a therapeutic agent.Curr Mol Med 17:46-59.
Frezzotti P,Giorgio A,Toto F,De Leucio A,De Stefano N(2016)Early changes of brain connectivity in primary open angle glaucoma.Hum Brain Mapp 37:4581-4596.
Gupta N,Ang LC,Noel de Tilly L,Bidaisee L,Yucel YH(2006)Human glaucoma and neural degeneration in intracranial optic nerve,lateral geniculate nucleus,and visual cortex.Br J Ophthalmol 90:674-678.
Lawlor M,Danesh-Meyer H,Levin LA,Davagnanam I,De Vita E,Plant GT(2018)Glaucoma and the brain:Trans-synaptic degeneration,structural change,and implications for neuroprotection.Surv Ophthalmol 63:296-306.
Murai H,Suzuki Y,Kiyosawa M,Tokumaru AM,Ishiwata K,Ishii K(2015)Cerebral glucose metabolism in the striate cortex positively correlates with fractional anisotropy values of the optic radiation in patients with glaucoma.Clin Exp Ophthalmol 43:711-719.
Murphy MC,Conner IP,Teng CY,Lawrence JD,Safiullah Z,Wang B,Bilonick RA,Kim SG,Wollstein G,Schuman JS,Chan KC(2016)Retinal structures and visual cortex activity are impaired prior to clinical vision loss in glaucoma.Sci Rep 6:31464.
Nuzzi R,Dallorto L,Rolle T(2018)Changes of visual pathway and brain connectivity in glaucoma:a systematic review.Front Neurosci 12:363.
Shimazawa M,Ito Y,Inokuchi Y,Yamanaka H,Nakanishi T,Hayashi T,Ji B,Higuchi M,Suhara T,Imamura K,Araie M,Watanabe Y,Onoe H,Hara H(2012)An alteration in the lateral geniculate nucleus of experimental glaucoma monkeys:in vivo positron emission tomography imaging of glial activation.PLoS One 7:e30526.
Sponsel WE,Groth SL,Satsangi N,Maddess T,Reilly MA(2014)Refined data analysis provides clinical evidence for central nervous system control of chronic glaucomatous neurodegeneration.Transl Vis Sci Technol 3:1.
Susanna R Jr,De Moraes CG,Cioffi GA,Ritch R(2015)Why Do People(Still)Go blind from glaucoma?Transl Vis Sci Technol 4:1.
Tham YC,Li X,Wong TY,Quigley HA,Aung T,Cheng CY(2014)Global prevalence of glaucoma and projections of glaucoma burden through2040:a systematic review and meta-analysis.Ophthalmology 121:2081-2090.
Trivedi V,Chen Y,Parra C,Arshad A,Bang JW,Wu M,Conner IP,Wollstein G,Schuman JS,Chan KC(2018)Evaluation of volumetric and diffusional brain changes and their associations with retinal structures and visual field function in glaucoma using MRI,OCT and perimetry.Invest Ophthalmol Vis Sci 59:3502.
van der Merwe Y,Yang X,Ho LC,Yu Y,Chau Y,Leung CK,Conner IP,Wollstein G,Schuman JS,Chan KC(2016)Citicoline preserves optic nerve integrity and visuomotor function following chronic intraocular pressure elevation.Invest Ophthalmol Vis Sci 57:3788-3800.
Wang R,Tang Z,Sun X,Wu L,Wang J,Zhong Y,Xiao Z(2018)White matter abnormalities and correlation with severity in normal tension glaucoma:a whole brain atlas-based diffusion tensor study.Invest Ophthalmol Vis Sci 59:1313-1322.
Yang XL,van der Merwe Y,Sims J,Parra C,Ho LC,Schuman JS,Wollstein G,Lathrop KL,Chan KC(2018)Age-related changes in eye,brain and visuomotor behavior in the DBA/2J mouse model of chronic glaucoma.Sci Rep8:4643.