Retinal and optic nerve diseases are degenerative ocular pathologies which lead to irreversible visual loss. Since the advanced therapies availability, cell-based therapies offer a new all-encompassing approach. Advan...Retinal and optic nerve diseases are degenerative ocular pathologies which lead to irreversible visual loss. Since the advanced therapies availability, cell-based therapies offer a new all-encompassing approach. Advances in the knowledge of neuroprotection, immunomodulation and regenerative properties of mesenchymal stem cells(MSCs) have been obtained by several preclinical studies of various neurodegenerative diseases. It has provided the opportunity to perform the translation of this knowledge to prospective treatment approaches for clinical practice. Since 2008, several first steps projecting new treatment approaches, have been taken regarding the use of cell therapy in patients with neurodegenerative pathologies of optic nerve and retina. Most of the clinical trials using MSCs are in Ⅰ/Ⅱ phase, recruiting patients or ongoing, and they have as main objective the safety assessment of MSCs using various routes of administration. However, it is important to recognize that, there is still a long way to go to reach clinical trials phase Ⅲ-Ⅳ. Hence, it is necessary to continue preclinical and clinical studies to improve this new therapeutic tool. This paper reviews the latest progress of MSCs in human clinical trials for retinal and optic nerve diseases.展开更多
Retinal degenerations are the leading causes of irreversible visual loss worldwide. Many pathologies included under this umbrella involve progressive degeneration and ultimate loss of the photoreceptor cells, with age...Retinal degenerations are the leading causes of irreversible visual loss worldwide. Many pathologies included under this umbrella involve progressive degeneration and ultimate loss of the photoreceptor cells, with age-related macular degeneration and inherited and ischemic retinal diseases the most relevant. These diseases greatly impact patients' daily lives, with accompanying marked social and economic consequences. However, the currently available treatments only delay the onset or slow progression of visual impairment, and there are no cures for these photoreceptor diseases. Therefore, new therapeutic strategies are being investigated, such as gene therapy, optogenetics, cell replacement, or cell-based neuroprotection. Specifically, stem cells can secrete neurotrophic, immunomodulatory, and anti-angiogenic factors that potentially protect and preserve retinal cells from neurodegeneration. Further, neuroprotection can be used in different types of retinal degenerative diseases and at different disease stages, unlike other potential therapies. This review summarizes stem cell-based paracrine neuroprotective strategies for photoreceptor degeneration, which are under study in clinical trials, and the latest preclinical studies. Effective retinal neuroprotection could be the next frontier in photoreceptor diseases, and the development of novel neuroprotective strategies will address the unmet therapeutic needs.展开更多
Retinal neurodegenerative diseases like agerelated macular degeneration,glaucoma,diabetic retinopathy or retinitis pigmentosa are the most frequent causes of incurable low vision and blindness worldwide.It had been es...Retinal neurodegenerative diseases like agerelated macular degeneration,glaucoma,diabetic retinopathy or retinitis pigmentosa are the most frequent causes of incurable low vision and blindness worldwide.It had been estimated that the prevalence of these diseases varies between 1/750 and 1/5000 depending on the region,the level of consanguinity or ethnicity(Na et al.,2017).The functional and structural complexity of the retina makes it susceptible to multiple types of pathogenic damage.展开更多
Diabetes mellitus is a leading cause of acquired vision loss and one of the world＇s fastest growing chronic diseases. Diabetic retinopathy （DR）, a specific complication of chronic hyperglycemia, is the leading caus...Diabetes mellitus is a leading cause of acquired vision loss and one of the world＇s fastest growing chronic diseases. Diabetic retinopathy （DR）, a specific complication of chronic hyperglycemia, is the leading cause of acquired vision loss worldwide in middle-aged and there- fore economically active people that also increases the medical and economic burden on the society （Klein, 2007）.展开更多
AIM: To assess the relationship between choroidal thickness and renal function in diabetic patients. METHODS: Cross-sectional retrospective clinical study of 42 eyes of 21 ocular treatment-na?ve diabetic patients. Dem...AIM: To assess the relationship between choroidal thickness and renal function in diabetic patients. METHODS: Cross-sectional retrospective clinical study of 42 eyes of 21 ocular treatment-na?ve diabetic patients. Demographic data included: age, sex, type and course of diabetes. Ocular data included: severity of diabetic retinopathy;retinal thickness at the central macular region, as well as choroidal thickness at the central and paracentral quadrants, using automatically generated maps by swept-source optical coherence tomography;presence of cystic macular edema;and ocular axial length(AXL). Lab-test parameters included: glycated hemoglobin(HbA1c), albuminuria, albumin/creatinine ratio in urine, and glomerular filtration rate. RESULTS: A significant negative correlation was mainly observed between several choroidal thicknesses, age(P<0.020) and ocular AXL(P<0.030). On the contrary, a significant positive correlation was found between all choroidal thicknesses, HbA1 c(P<0.035) and albuminuria(P<0.040). CONCLUSION: Choroidal thickness can represent an additional tool to help clinicians predicting the renal status in ocular treatment-na?ve diabetic patients.展开更多
Background Different ocular alterations have been described in patients with coronavirus disease 2019(COVID-19).Our aim was to determine whether COVID-19 affected retinal cells and establish correlations with clinical...Background Different ocular alterations have been described in patients with coronavirus disease 2019(COVID-19).Our aim was to determine whether COVID-19 affected retinal cells and establish correlations with clinical parameters.Methods Retinal sections and flat-mount retinas from human donors with COVID-19(n=16)and controls(n=15)were immunostained.The location of angiotensin-converting enzyme 2(ACE2)and the morphology of microglial cells,Muller cells,astrocytes,and photoreceptors were analyzed by confocal microscopy.Microglial quantification and the area occupied by them were measured.Correlations among retinal and clinical parameters were calculated.Results ACE2 was mainly located in the Muller cells,outer segment of cones and retinal pigment epithelium.Cell bodies of Muller cells in COVID-19 group showed greater staining of ACE2 and cellular retinaldehyde-binding protein(CRALBP).The 81.3%of COVID-19 patients presented disorganization of honeycomb-like pattern formed by Muller cells.Gliosis was detected in 56.3%of COVID-19 patients compared to controls(40%)as well as epiretinal membranes(ERMs)or astrocytes protruding(50%).Activated or ameboid-shape microglia was the main sign in the COVID-19 group(93.8%).Microglial migration towards the vessels was greater in the COVID-19 retinas(P<0.05)and the area occupied by microglia was also reduced(P<0.01)compared to control group.Cone degeneration was more severe in the COVID-19 group.Duration of the disease,age and respiratory failure were the most relevant clinical data in relation with retinal degeneration.Conclusions The retinas of patients with COVID-19 exhibit glial activation and neuronal alterations,mostly related to the inflammation,hypoxic conditions,and age.展开更多
基金Supported by A grants from the Consejería de Educación de la Junta de Castilla y León,No.VA118U14the Centro en Red de Medicina Regenerativa y Terapia Celular de la Junta de Castilla y León,47011 Valladolid
文摘Retinal and optic nerve diseases are degenerative ocular pathologies which lead to irreversible visual loss. Since the advanced therapies availability, cell-based therapies offer a new all-encompassing approach. Advances in the knowledge of neuroprotection, immunomodulation and regenerative properties of mesenchymal stem cells(MSCs) have been obtained by several preclinical studies of various neurodegenerative diseases. It has provided the opportunity to perform the translation of this knowledge to prospective treatment approaches for clinical practice. Since 2008, several first steps projecting new treatment approaches, have been taken regarding the use of cell therapy in patients with neurodegenerative pathologies of optic nerve and retina. Most of the clinical trials using MSCs are in Ⅰ/Ⅱ phase, recruiting patients or ongoing, and they have as main objective the safety assessment of MSCs using various routes of administration. However, it is important to recognize that, there is still a long way to go to reach clinical trials phase Ⅲ-Ⅳ. Hence, it is necessary to continue preclinical and clinical studies to improve this new therapeutic tool. This paper reviews the latest progress of MSCs in human clinical trials for retinal and optic nerve diseases.
基金supported by Fundación Carolina,Madrid,SpainFondo Europeo de Desarrollo Regional,Fondo Social Europeo and Consejería de Educación(Grant VA077P17),Junta de Castilla y León,SpainCentro en Red de Medicina Regenerativa y Terapia Celular,Junta de Castilla y León,Spain,respectively
文摘Retinal degenerations are the leading causes of irreversible visual loss worldwide. Many pathologies included under this umbrella involve progressive degeneration and ultimate loss of the photoreceptor cells, with age-related macular degeneration and inherited and ischemic retinal diseases the most relevant. These diseases greatly impact patients' daily lives, with accompanying marked social and economic consequences. However, the currently available treatments only delay the onset or slow progression of visual impairment, and there are no cures for these photoreceptor diseases. Therefore, new therapeutic strategies are being investigated, such as gene therapy, optogenetics, cell replacement, or cell-based neuroprotection. Specifically, stem cells can secrete neurotrophic, immunomodulatory, and anti-angiogenic factors that potentially protect and preserve retinal cells from neurodegeneration. Further, neuroprotection can be used in different types of retinal degenerative diseases and at different disease stages, unlike other potential therapies. This review summarizes stem cell-based paracrine neuroprotective strategies for photoreceptor degeneration, which are under study in clinical trials, and the latest preclinical studies. Effective retinal neuroprotection could be the next frontier in photoreceptor diseases, and the development of novel neuroprotective strategies will address the unmet therapeutic needs.
基金This work was supported by grant from Fondo Europeo de Desarrollo RegionalFondo Social EuropeoConsejería de Educación from Junta de Castilla y León,Spain(VA077P17).
文摘Retinal neurodegenerative diseases like agerelated macular degeneration,glaucoma,diabetic retinopathy or retinitis pigmentosa are the most frequent causes of incurable low vision and blindness worldwide.It had been estimated that the prevalence of these diseases varies between 1/750 and 1/5000 depending on the region,the level of consanguinity or ethnicity(Na et al.,2017).The functional and structural complexity of the retina makes it susceptible to multiple types of pathogenic damage.
基金supported by EU Program FP7-PEOPLE-2013-IAPP(612218/3D-NET)FEDER-CICYT MAT2013-47501-CO2-1-R(Ministry of Economy and Competitiveness,Spain)Grants+1 种基金supported by RETICS(RD12/0034/0001)Instituto de Salud CarlosⅢ,Spain
文摘Diabetes mellitus is a leading cause of acquired vision loss and one of the world＇s fastest growing chronic diseases. Diabetic retinopathy （DR）, a specific complication of chronic hyperglycemia, is the leading cause of acquired vision loss worldwide in middle-aged and there- fore economically active people that also increases the medical and economic burden on the society （Klein, 2007）.
基金OFTARED “RD16/0008/0010”,funded by Instituto de Salud Carlos Ⅲ,integrated in the national I+D+i 2013-2016co-funded by European Union(ERDF/ESF,“Investing in your future”)
文摘AIM: To assess the relationship between choroidal thickness and renal function in diabetic patients. METHODS: Cross-sectional retrospective clinical study of 42 eyes of 21 ocular treatment-na?ve diabetic patients. Demographic data included: age, sex, type and course of diabetes. Ocular data included: severity of diabetic retinopathy;retinal thickness at the central macular region, as well as choroidal thickness at the central and paracentral quadrants, using automatically generated maps by swept-source optical coherence tomography;presence of cystic macular edema;and ocular axial length(AXL). Lab-test parameters included: glycated hemoglobin(HbA1c), albuminuria, albumin/creatinine ratio in urine, and glomerular filtration rate. RESULTS: A significant negative correlation was mainly observed between several choroidal thicknesses, age(P<0.020) and ocular AXL(P<0.030). On the contrary, a significant positive correlation was found between all choroidal thicknesses, HbA1 c(P<0.035) and albuminuria(P<0.040). CONCLUSION: Choroidal thickness can represent an additional tool to help clinicians predicting the renal status in ocular treatment-na?ve diabetic patients.
基金supported from grants funded by the Spanish Ministry of Science and Innovation(FEDER-PID2019-106230RB-I00)Spanish Ministry of Universities(FPU16/04114 and FPU18/02964)+2 种基金National Institute of Health Carlos III(RETICS-FEDER RD16/0008/0016)Generalitat Valenciana(IDIFEDER/2017/064,PROMETEO/2021/024)Valencia University General Hospital Foundation.
文摘Background Different ocular alterations have been described in patients with coronavirus disease 2019(COVID-19).Our aim was to determine whether COVID-19 affected retinal cells and establish correlations with clinical parameters.Methods Retinal sections and flat-mount retinas from human donors with COVID-19(n=16)and controls(n=15)were immunostained.The location of angiotensin-converting enzyme 2(ACE2)and the morphology of microglial cells,Muller cells,astrocytes,and photoreceptors were analyzed by confocal microscopy.Microglial quantification and the area occupied by them were measured.Correlations among retinal and clinical parameters were calculated.Results ACE2 was mainly located in the Muller cells,outer segment of cones and retinal pigment epithelium.Cell bodies of Muller cells in COVID-19 group showed greater staining of ACE2 and cellular retinaldehyde-binding protein(CRALBP).The 81.3%of COVID-19 patients presented disorganization of honeycomb-like pattern formed by Muller cells.Gliosis was detected in 56.3%of COVID-19 patients compared to controls(40%)as well as epiretinal membranes(ERMs)or astrocytes protruding(50%).Activated or ameboid-shape microglia was the main sign in the COVID-19 group(93.8%).Microglial migration towards the vessels was greater in the COVID-19 retinas(P<0.05)and the area occupied by microglia was also reduced(P<0.01)compared to control group.Cone degeneration was more severe in the COVID-19 group.Duration of the disease,age and respiratory failure were the most relevant clinical data in relation with retinal degeneration.Conclusions The retinas of patients with COVID-19 exhibit glial activation and neuronal alterations,mostly related to the inflammation,hypoxic conditions,and age.
