Having a family history (FH+) of Alzheimer's disease (AD) and being a carrier of at least one ɛ4 allele of the ApoE gene are two of the main risk factors for the development of AD. AD and age-related ...macular degeneration (AMD) share one of the main risk factors, such as age, and characteristics including the presence of deposits (Aβ plaques in AD and drusen in AMD); however, the role of apolipoprotein E isoforms in both pathologies is controversial. We analyzed and characterized retinal drusen by optical coherence tomography (OCT) in subjects, classifying them by their AD FH (FH- or FH+) and their allelic characterization of ApoE ɛ4 (ApoE ɛ4- or ApoE ɛ4+) and considering cardiovascular risk factors (hypercholesterolemia, hypertension, and diabetes mellitus). In addition, we analyzed the choroidal thickness by OCT and the area of the foveal avascular zone with OCTA. We did not find a relationship between a family history of AD or any of the ApoE isoforms and the presence or absence of drusen. Subjects with drusen show choroidal thinning compared to patients without drusen, and thinning could trigger changes in choroidal perfusion that may give rise to the deposits that generate drusen.
Purpose
Alzheimer’s disease is the most common cause of dementia. In addition to the age,a family history (FH+) of AD and ɛ4 allele of the ApoE gene are the main genetic risk factors for developing ...the disease. However, ɛ4 allele of ApoE plays a protective role in age‐related macular degeneration. In both pathologies vascular changes have been reported in the retina and the choroid. The aim of this study was analyzed ocular vascular changes in subject with high genetic risks for developing AD.
Methods
A complete eye examination was carried out in 184 cognitively healthy subjects. We analyzed the choroidal thickness using optical coherence tomography (OCT) and the foveal avascular zone (FAZ) using OCT‐angiography (OCTA) and compared the results with ApoE gene expression, AD FH+, and the presence or absence of hard drusen (HD).
Results
Choroidal thickness was statistically significantly different (p < 0.05) in the (FH‐, ɛ4‐, HD+) group compared with: (i) both the (FH‐, ɛ4‐, HD‐) and the (FH+, ɛ4+, HD+) groups in the superior and inferior points at 1500 μm, and (ii) the (FH+, ɛ4‐, HD+) group in the superior point at 1500 μm, There were statistically significant differences (p < 0.05) in the superficial FAZ between the (FH+, ɛ4‐, HD+) group and i) the (FH+, ɛ4‐, HD‐) group and ii) the (FH+, ɛ4+, HD‐) group.
Conclusions
In conclusion, ocular vascular changes have not yet been found in participants at genetic risk of developing AD; however, subjects without genetic risk of AD who have HD should be followed for their evolution.
Purpose
Alzheimer's disease (AD) is a progressive neurodegeneration in which vascular changes occur that constitute cerebral amyloid angiopathy. Recently, alterations and deposits have been ...discovered in the retinas and choroids of patients with AD that correlate with the evolution of the disease. The development of new techniques for the study of ocular vascularization, Laguna ONhE and Angio‐optical coherence tomography (OCTA), non‐invasive and non‐contrast tests, allow us to study ocular vascular alterations caused by AD.
Methods
Seventeen patients with mild AD (mAD) and 49 healthy controls, all without ophthalmological diseases after a complete eye examination, were studied for haemoglobin (Hb) coefficient in the optic nerve head by Laguna ONhE, as well as choroid thickness and foveal avascular zone (FAZ) of the retina by OCTA. For statistical analysis, the Mann‐Whitney test was applied with the SPSS 22.00 program.
Results
The Mini Mental State Examination of the mAD patients was 24.00 ± 5.32, while the control group was 29.40 ± 1.83, being the difference significant (p < 0.001) between them. Comparing both group, no significant difference was found in the Hb coefficient of the optic nerve head, although in the papillomacular bundle, there was a slight increase of Hb coefficient in mAD patients. A significant (p < 0.05) thinning of the choroid was found in the mAD patients, while the FAZ was unchanged in comparison to control.
Conclusions
In patients with mAD, a significant decrease in the choroidal vascular network was observed, while the retinal network and the Hb of the optic nerve head did not yet show any changes in mild stages of AD. These results show the choroidal changes as an early biomarker of amyloid angiopathy that could be used for the diagnosis and follow‐up of AD.
Alzheimer's disease (AD) is a neurodegenerative dementia characterized by the deposition of extracellular β-amyloid (Aβ) plaques and the presence of neurofibrillary tangles. Until now, the techniques ...used to analyze these deposits have been difficult to access, invasive, and expensive. This leads us to consider new access routes to the central nervous system (CNS), allowing us to diagnose the disease before the first symptoms appear. Recent studies have shown that microglial and macroglial cell activation could play a role in the development of this disease. Glial cells in the CNS can respond to various damages, such as neurodegenerative pathologies, with morphological and functional changes. These changes are a common feature in neurodegenerative diseases, including AD. The retina is considered an extension of the CNS and has a population of glial cells similar to that of the CNS. When glial cells are activated, various molecules are released and changes in glial cell expression occur, which can be indicators of neuronal damage. The objective of this review is to compile the most relevant findings in the last 10 years relating to alterations in the eye in AD, and the role that glial cells play in the degenerative process in the retina in the context of neurodegeneration.
La enfermedad de Alzheimer (EA) es una demencia neurodegenerativa que se caracteriza por la deposición de placas beta-amiloides (βA) extracelulares, y la presencia de ovillos neurofibrilares. Hasta ahora, las técnicas utilizadas para analizar estos depósitos han sido poco accesibles, invasivas y costosas. Esto nos lleva a considerar nuevas vías de acceso al sistema nervioso central (SNC) que nos permitan diagnosticar la enfermedad antes de la aparición de sus primeros síntomas. Los estudios recientes han reflejado que la activación de las células microgliales y macrogliales podría desempeñar un papel en el desarrollo de esta enfermedad. Las células gliales del SNC pueden responder a diversos daños, tales como patologías neurodegenerativas, con cambios morfológicos y funcionales. Dichos cambios son una característica común en las enfermedades neurodegenerativas, incluyendo la EA. La retina se considera una extensión del SNC, y cuenta con una población de células gliales similar a la de dicho sistema. Cuando las células gliales se activan, se liberan diversas moléculas, y se producen diversos cambios en la expresión de las células gliales, que pueden ser indicadores de daño neuronal. El objetivo de esta revisión es recopilar los hallazgos más relevantes de los últimos diez años, con relación a las alteraciones oculares en la EA, y el papel que juegan las células gliales en el proceso degenerativo de la retina en el contexto de la neurodegeneración.
Purpose
Alzheimer’s diseases (AD) is the most common cause of dementia characterized by a progressive decline in cognitive function, especially in the memory domain. It is known that its signs can ...appear decades before to clinical symptoms. In addition to age, genetic studies have identified an association between the presence of the Apoliprotein (ApoE) ɛ4 allele and family history of disease with the late‐onset AD. The aim of the present study was analyzed the possible changes that may occur in visual acuity (VA) and contrast sensitive test (CST) in young subjects with two marked genetic factors risk of developing Alzheimer’s (AD): a first‐degree family history of the disease and being carrier of at least one e4 allele for the ApoE gene.
Methods
A case‐control study was conducted in 28 subjects with family history of AD (FH+), ApoE ɛ4 carriers and with a mean age of 53.39 years and 16 age‐matched control subjects without a family history of AD (FH‐), ApoE ɛ4 non‐carriers and with a mean age of 53.94 years. A complete eye examination was performed in all participants, who were free of ocular pathology.
Results
We found statistical significant increase (p < 0.05) in FH+ ApoE ɛ4 carriers compared to FH‐ ApoE ɛ4 non‐carriers in: I) VA (1.04 ± 0.10, FH+ vs 0.98 ± 0.04, FH‐) and II) CS in the spatial frequency (SF) of 12 cycles/degree (1.68 ± 0.18, FH+ vs 1.54 ± 0.17, FH‐).
Conclusions
In FH+ ApoE ɛ4 carriers, the VA and CST registered changes compared to FH‐ ApoE ɛ4 non‐carriers. In young subjects at high genetic risk of developing AD, an increase of VA and CS in the 12 cicles/degree SF could be the first functional changes to appear.
Purpose
Alzheimer’s diseases is a neurodegenerative disease, whose signs can appear decades before clinically detectable symptoms. In addition to age, genetic factors are one of the most important ...risk factors. The aim of the present study was analyzed the macular thickness changes by optical coherence tomography (OCT) in subjects who have a first‐degree family history of AD and are carriers of ɛ4 allele for the ApoE, which are two of the main risk factors for developing the disease.
Methods
A complete eye examination and a macular OCT were performed in 64 participants, who were free of ocular pathology. The two study groups were formed by 35 subjects with a family history of AD (FH+) and ApoE ɛ4 carriers and 29 age‐matched control subjects without a family history of AD (FH‐) and ApoE ɛ4 non‐carriers.
Results
We found a statistical significant thinning (p < 0.05) in FH+ ApoE ɛ4 carriers compared to FH‐ ApoE ɛ4 non‐carriers in the next sectors and layers: the foveal area of the macular retinal nerve fiber layer (11.89 ± 1.95, FH+ vs 12.86 ± 1.62, FH‐); the inferior and nasal sectors, both in the outer (26.77 ± 2.74, FH+ vs 28.17 ± 2.82, FH‐) (29.49 ± 2.89, FH+ vs 30.93 ± 3.85, FH‐) and inner (40.49 ± 2.51, FH+ vs 42.10 ± 3.48, FH‐) (41.94 ± 2.74, FH+ vs 43.52 ± 3.57, FH‐) macular ring in the inner plexiform layer; the foveal area (18.82 ± 3.61, FH+ vs 21.21 ± 3.88, FH‐) and the inferior sector in the outer macular ring (30.91 ± 2.72, FH+ vs 32.10 ± 2.81, FH‐) in inner nuclear layer, and the inferior sector of the outer macular ring (27.60 ± 2.75, FH+ vs 29.97 ± 3.82, FH‐) in outer plexiform layer.
Conclusions
The slight retinal thickness changes measured by OCT, that appear in the macular area in asymptomatic subjects at high genetic risk for the development of AD, could be used as an early biomarker of the disease.
Purpose
To analyze microglial cells activation features, and P2RY12, MHC‐II and CD68 expression in 15‐month‐old mice compared to young adult mice, after unilateral laser‐induced ocular hypertension ...(OHT)
Methods
Albino Swiss mice divided in four groups; young naïve (n = 6), aged naïve (n = 6), young OHT (YG) (n = 6) and aged OHT (AG) (n = 6), were analyzed. In OHT groups, both OHT eyes and contralateral eyes were studied. Retinal whole‐mounts were processed with: 1) anti Iba‐1 to quantify: i) Iba‐1 + cells number (Ibacn) in outer segments (OS), outer plexiform layer (OPL) and inner plexiform layer (IPL); ii) area of retina occupied by Iba‐1 + cells (Iba‐1 RA) in the nerve fiber layer‐ ganglion cell layer (NFL‐GCL) iii) cell body area of Iba‐1+ cells (CbIbac) in OPL, IPL and NFL‐GCL; iv) arbor area of Iba‐1+ cells (AAIbac) in OPL and IPL; and vi) vertical processes number of Iba‐1+ cells (VPIbac) between OS and OPL. 2) anti‐P2RY12, (resident microglia), anti‐CD68 (phagocytic activity) and anti‐MHC‐II (microglial activation marker)
Results
Both OHT eyes and contralateral eyes of YG and AG showed significant: increase of Ibacn, Iba‐1 RA, CbIbac and VPIbac and decrease of AAIbac, more pronounced in OHT eyes, compared to their respective naïve groups. Comparing YG and AG showed: i) AG versus YG in OHT eyes, significant decrease of Iba‐1 RA and VPIbac; ii) AG versus YG in contralateral eyes, a significant increase of Ibacn (OS) and a significant decrease of CbIbac and AAIbac (IPL). Analyzing the P2RY12, CD68 and MHC‐II expression we observed: i) in YG all Iba‐1+ cells were P2RY12+, except perivascular and dendritic cells, but in AG most cells were Iba‐1+/P2RY12‐; ii) in AG and YG numerous amoeboid‐like CD68+ cells were found but in AG ramified appearance CD68+ cells were also observed, and iii) While in YG practically all Iba‐1+ cells were MHC‐II+, in AG some Iba‐1+ cells showed MHC‐II+ expression
Conclusions
The morphological and molecular differences found in microglial cells of AG compared to YG show the possible aging implication in glaucoma.
Purpose
Alzheimer' disease (AD) is a neurodegenerative brain pathology, characterized by a loss of neuron and their synapses. Similar changes have been found in the retina even before appeared in the ...brain. The retina has been postulated as an accessible biomarker of AD. The aim of this study was to analyze changes in retinal thickness over time in a mouse model of AD (APPNL‐F/NL‐F).
Methods
Retinas of male APPNL‐F/NL‐F (n = 55) and WT (n = 39) animals were evaluated in vivo by SD‐OCT at 6, 9, 12, 15, 17 and 20 months old. The mean total retinal thickness was analysed following the ETDRS sectors. To analyse the RNFL, axonal ring scan around the optic nerve head was carried out. RNFL was measured in six sectors provided by the manufacturer. Only the left eyes were used to study.
Results
In the APPNL‐F/NL‐F group compared to WT animals, the total retinal thickness showed a slight thinning up to the 15 months old, this being significant only at 6 months in the outer temporal ring. At 17 months, there was thickening in the total retinal thickness being significant in the inferior and nasal sectors, both in inner and outer rings. At 20 months, there was a significant thinning in superior and temporal retina, both in inner and outer rings. RNFL thickness showed similar changes, that being only significates, the thinning in the global analysis and in nasal and inner‐temporal sectors at 6 months old.
Conclusions
In the mouse model of AD (APPNL‐F/NL‐F), there is a thinning of the retinal thickness up to 15 months, followed by a thickening at 17 months and a subsequent thinning at 20 months in some retinal areas. These changes over time are similar to those observed in the human retina, with areas of thinning, possibly caused by neurodegeneration, followed by thickening, possibly caused by deposits and neuroinflammation; this experimental AD model could help for an extensive understanding of the different retinal changes during the AD progression.
Microglial changes in healthy mice retina in an early aging stage Fernández‐Albarral, José A.; Salobrar‐Garcia, Elena; López‐Cuenca, Inés ...
Acta ophthalmologica (Oxford, England),
January 2021, 2021-01-00, 20210101, Letnik:
99, Številka:
S265
Journal Article
Recenzirano
Purpose
To quantify different morphological signs of microglial cells activation, as well as to analyze the P2RY12, MHC‐II and CD68 expression in 15‐month old mice , an early stage of aging (aged ...naïve) in comparison with a young adult mice (young naïve).
Methods
Young naïve (n = 6) and aged naïve (n = 6) mice were analyzed. Retinal whole‐mounts were immunolabeled with: 1) anti Iba‐1 to quantify: i) Iba‐1 + cells number (Ibacn) in outer segments (OS), outer plexiform layer (OPL) and inner plexiform layer (IPL); ii) area of retina occupied by Iba‐1 + cells (Iba‐1 RA) in the nerve fiber layer‐ ganglion cell layer (NFL‐GCL) iii) cell body area of Iba‐1+ cells (CbIbac) in OPL, IPL and NFL‐GCL; iv) arbor area of Iba‐1+ cells (AAIbac) in OPL and IPL; number of vertical processes of Iba‐1+ cells (VPIbac) beetween the OS and OPL. 2) anti‐P2RY12 to identify resident microglia, anti‐CD68 and anti‐MHC‐II as a microglial activation marker.
Results
In aged naïve with respect to young naïve the quantitative analysis showed: i) a non‐significant increase in the Ibacn in OS; ii) a non‐significant decrease in the AAIbac in OPL; iii) a significant increase in the CbIbac in OPL, IPL and NFL‐GCL and iv) a significant increase in the VPIbac. When we analyzed the expression of P2RY12, CD68 and MHC‐II we observed: i) in young naïve all Iba‐1+ cells were P2RY12+, except perivascular and dendritic cells, but in the aged naïve some cells were Iba‐1+/P2RY12‐; ii) in aged naïve numerous amoeboid‐like CD68+ cells were found while in the young naïve the expression of CD68 practically was absent, and iii) in both young naïve and aged naïve no expression of MHC‐II was observed.
Conclusions
In 15‐month‐old mice, morphological changes and in the expression of P2RY12, CD68 and MHC‐II occurs in the microglial cells compared to young adult mice. These signs show a non‐pathological state of microglial activation that could influence of retinal age‐related disorders.
Retinal microglial activation in a SOD1 mouse model of ALS Pilar Rojas Lozano, María; Cadena Santoyo, Manuel; Fernández‐Albarral, José A. ...
Acta ophthalmologica (Oxford, England),
January 2021, 2021-01-00, 20210101, Letnik:
99, Številka:
S265
Journal Article
Recenzirano
Purpose
To determine the differences in retinal microglial behaviour in a SOD1G93A mouse model (SOD) of amyotrophic lateral sclerosis (ALS) compared to the wild type (WT).
Methods
In retinal ...whole‐mounts labelled with anti‐Iba‐1 (microglial marker) from two experimental groups WT (n = 6) and SOD ALS (n = 6), signs of microglial activation were quantified in different retinal layers: (i) Iba‐1 + cells number in outer segments (OS), outer plexiform layer (OPL) and inner complex layer (ICL) constituted by inner plexiform layer (IPL), ganglion cell layer (GCL) and retinal nerve fiber layer (RNFL); (ii) cell area of Iba‐1+ cells in OPL and IPL; (iii) arbor area of Iba‐1+ cells in OPL and IPL. Animals were sacrificed with 120 days old.
Results
Compared to WT, the retina of SOD1 ALS mice showed: (i) Migrations and reorientation processes of some Iba‐1 + cells; (ii) A significant increase in the Iba‐1 + cell area in OPL (in inferior, nasal, temporal regions and total number) and in the total number in IPL; (iii) A significant increase in the arbor area in the inferior OPL region; (iv) No significant changes were observed in the number of Iba‐1 + cells in OS, OPL and ICL.
Conclusions
These findings demonstrate a non‐proliferative microgliosis in SOD1‐ALS mice retinas. The microglial activation was higher in OPL, which could be related to an increased inflammatory process in this retinal layer. Although ALS is a motor neuron disease, it can also affect the retinal tissue where an inflammatory process takes place.
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