-
Translational Vision Science &... Jun 2024Both hypertension and diabetes are known to increase the wall-to-lumen ratio (WLR) of retinal arterioles, but the differential effects are unknown. Here, we study the...
PURPOSE
Both hypertension and diabetes are known to increase the wall-to-lumen ratio (WLR) of retinal arterioles, but the differential effects are unknown. Here, we study the timing and relative impact of hypertension versus diabetes on the WLR in diabetic retinopathy (DR) to address this unresolved question.
METHODS
This prospective cross-sectional study compared the retinal arteriolar WLR in 17 healthy eyes, 15 with diabetes but no apparent DR (DM no DR), and 8 with diabetic macular edema (DME) and either nonproliferative or proliferative DR. We imaged each arteriole using adaptive optics scanning laser ophthalmoscopy and measured the WLR using ImageJ. Multiple linear regression (MLR) was performed to estimate the effects of hypertension, diabetes, and age on the WLR.
RESULTS
Both subjects with DM no DR and subjects with DME had significantly higher WLR than healthy subjects (0.36 ± 0.08 and 0.42 ± 0.08 vs. 0.29 ± 0.07, 1-way ANOVA P = 0.0009). MLR in healthy subjects and subjects with DM no DR showed hypertension had the strongest effect (regression coefficient = 0.08, P = 0.009), whereas age and diabetes were not significantly correlated with WLR. MLR in all three groups together (healthy, DM no DR, and DME) showed diabetes had the strongest effect (regression coefficient = 0.05, P = 0.02), whereas age and hypertension were not significantly correlated with WLR.
CONCLUSIONS
Hypertension may be an early driver of retinal arteriolar wall thickening in preclinical DR, independent of age or diabetes, whereas changes specific to DR may drive wall thickening in DME and later DR stages.
TRANSLATIONAL RELEVANCE
We offer a framework for understanding the relative contributions of hypertension and diabetes on the vascular wall, and emphasize the importance of hypertension control early in diabetes even before DR onset.
Topics: Humans; Cross-Sectional Studies; Male; Diabetic Retinopathy; Female; Middle Aged; Prospective Studies; Arterioles; Hypertension; Ophthalmoscopy; Aged; Adult; Retinal Artery; Macular Edema
PubMed: 38874974
DOI: 10.1167/tvst.13.6.8 -
Investigative Ophthalmology & Visual... Jun 2024To examine if changes in hemodynamic measures during an orthostatic challenge were associated with progression of age-related macular degeneration (AMD) over a 4-year...
PURPOSE
To examine if changes in hemodynamic measures during an orthostatic challenge were associated with progression of age-related macular degeneration (AMD) over a 4-year period in The Irish Longitudinal Study on Ageing.
METHODS
Participants with AMD who underwent an active stand (AS) test at wave 1 (2009/2010) and retinal photographs at both wave 1 and wave 3 (2014/2015) were included (N = 159: 121 with no AMD progression and 38 with progression). Beat-to-beat hemodynamic data were non-invasively collected using a Finometer MIDI device during the AS at wave 1, recording systolic blood pressure (sBP), diastolic blood pressure (dBP), mean arterial pressure (MAP), and heart rate. Cardiac output, stroke volume, and total peripheral resistance (TPR) were derived from these measures. Baseline characteristics were compared between groups with and without AMD progression. Mixed-effects linear regression models were used to assess the association between changes in hemodynamic parameters during the AS and AMD progression, controlling for known AMD-associated risk factors.
RESULTS
At baseline, increasing age and lower dBP were significantly associated with AMD progression. Mixed-effects models for the period between standing and 10 seconds post-stand revealed significant associations with AMD progression with a steeper drop in dBP and a slower drop in TPR. Between 10 and 20 seconds post-stand, AMD progression was significantly associated with less pronounced reduction in heart rate.
CONCLUSIONS
These observational data suggest that impaired hemodynamic responses within the first 20 seconds of orthostasis may be associated with the progression of AMD.
Topics: Humans; Male; Female; Disease Progression; Aged; Macular Degeneration; Ireland; Heart Rate; Aging; Blood Pressure; Longitudinal Studies; Autonomic Nervous System; Aged, 80 and over; Hemodynamics; Middle Aged; Risk Factors
PubMed: 38874963
DOI: 10.1167/iovs.65.6.24 -
Molecular Biology Reports Jun 2024Human Amniotic Membrane (hAM) is endowed with several biological activities and might be considered an optimal tool in surgical treatment for different ophthalmic...
BACKGROUND
Human Amniotic Membrane (hAM) is endowed with several biological activities and might be considered an optimal tool in surgical treatment for different ophthalmic pathologies. We pioneered the surgical use of hAM to treat retinal pathologies such as macular holes, tears, and retinal detachments, and to overcome photoreceptor damage in age-related macular degeneration. Although hAM contributed to improved outcomes, the mechanisms of its effects are not yet fully understood. The characterization and explanation of the effects of hAM would allow the adoption of this new natural product in different retinal pathologies, operative contexts, and hAM formulations. At this end, we studied the properties of a hAM extract (hAME) on the ARPE-19 cells.
METHODS AND RESULTS
A non-denaturing sonication-based technique was developed to obtain a suitable hAME. Viability, proliferation, apoptosis, oxidative stress, and epithelial-mesenchymal transition (EMT) were studied in hAME-treated ARPE-19 cells. The hAME was able to increase ARPE-19 cell viability even in the presence of oxidative stress (HO, TBHP). Moreover, hAME prevented the expression of EMT features, such as EMT-related proteins, fibrotic foci formation, and migration induced by different cytokines.
CONCLUSIONS
Our results demonstrate that the hAME retains most of the properties observed in the whole tissue by others. The hAME, other than providing a manageable research tool, could represent a cost-effective and abundant drug to treat retinal pathologies in the future.
Topics: Humans; Amnion; Cell Line; Retinal Pigment Epithelium; Cell Survival; Apoptosis; Oxidative Stress; Cell Proliferation; Epithelial-Mesenchymal Transition; Tissue Extracts
PubMed: 38874663
DOI: 10.1007/s11033-024-09647-7 -
Frontiers in Aging Neuroscience 2024Observational studies have reported inconsistent results on the relationship between chronic kidney disease (CKD) and age-related macular degeneration (AMD). The primary...
PURPOSE
Observational studies have reported inconsistent results on the relationship between chronic kidney disease (CKD) and age-related macular degeneration (AMD). The primary objective of this study was to investigate the causal relationships between estimated glomerular filtration rate (eGFR), CKD, its common causes, and AMD among participants of European descent.
METHODS
Genetic variants associated with eGFR, CKD and its common causes, encompassing diabetic nephropathy (DN), immunoglobulin A nephropathy (IgAN), and membranous nephropathy (MN) were obtained from previously published genome-wide association studies (GWAS) and FinnGen database. Summary statistics for early AMD, AMD, dry AMD, and wet AMD were acquired from the GWAS and FinnGen database. Inverse-variance-weighted (IVW) method was the main MR analysis. Sensitivity analyses were performed with Cochran's Q, MR-Egger intercept, and leave-one-out analysis. In addition, RadialMR was utilized to identify and remove outliers.
RESULTS
IVW results showed that CKD, eGFR were not associated with any type of AMD ( > 0.05). DN (OR: 1.042, 95% CI: 1.002-1.083, = 0.037) and MN (OR: 1.023, 95% CI: 1.007-1.040, = 0.005) were associated with an increased risk of earl AMD. DN (OR: 1.111, 95% CI: 1.07-1.154, = 4.87 × 10), IgAN (OR: 1.373, 95% CI: 1.097-1.719, = 0.006), and MN (OR: 1.036, 95% CI: 1.008-1.064, = 0.012) were associated with an increased risk of AMD. DN (OR: 1.090, 95% CI: 1.042-1.140, = 1.57 × 10) and IgAN (OR: 1.480, 95% CI: 1.178-1.858, = 7.55 × 10) were associated with an increased risk of dry AMD. The risk of wet AMD was associated with DN (OR: 1.107, 95% CI: 1.043-1.174, = 7.56 × 10) and MN (OR: 1.071, 95% CI: 1.040-1.103, = 5.48 × 10).
CONCLUSION
This MR study found no evidence of causal relationship between CKD and AMD. DN, IgAN, and MN may increase risk of AMD. This findings underscore the importance of ocular examinations in patients with DN, MN, and IgAN. More studies are needed to support the findings of our current study.
PubMed: 38872627
DOI: 10.3389/fnagi.2024.1399666 -
Scientific Reports Jun 2024We identified characteristics of patients with subretinal fluid (SRF) in macular edema (ME) secondary to branch retinal vein occlusion (BRVO) and determined their...
We identified characteristics of patients with subretinal fluid (SRF) in macular edema (ME) secondary to branch retinal vein occlusion (BRVO) and determined their clinical outcomes after anti-vascular endothelial growth factor (VEGF) treatment. Fifty-seven eyes of BRVO patients with ME were divided into two groups according to the presence or absence of SRF at diagnosis. We compared the aqueous profiles, ocular and systemic characteristics at baseline, and the clinical outcomes. The SRF group had significantly greater central subfield thickness (CST) values and poorer best-corrected visual acuity (BCVA) at baseline compared to the non-SRF group. The former group had significantly higher aqueous levels of interleukin-8, VEGF, and placental growth factor. CST reduction and BCVA improvement during treatment were significantly greater in the SRF group than in the non-SRF group. Consequently, CST values were significantly lower in the SRF group than in the non-SRF group at 12 months, when BCVA did not differ significantly between the two groups. The SRF group required more frequent anti-VEGF treatment over 12 months and exhibited a higher rate of macular atrophy. Based on the aqueous profiles and the number of treatments required, the presence of SRF in BRVO patients appears to be associated with higher disease activity.
Topics: Humans; Retinal Vein Occlusion; Macular Edema; Male; Female; Aged; Subretinal Fluid; Middle Aged; Visual Acuity; Vascular Endothelial Growth Factor A; Tomography, Optical Coherence; Angiogenesis Inhibitors; Aged, 80 and over
PubMed: 38871805
DOI: 10.1038/s41598-024-64047-y -
Stem Cell Research Aug 2024The Stargardt's Disease, Type 1 (STGD1) is associated with the loss of function mutations in ABCA4. This gene codes for a retina-specific, ATP-binding cassette (ABC)...
Generation and characterization of a Stargardt's disease-specific induced pluripotent stem cell line (LVPEIi008-A) with a homozygous nonsense mutation in exon 44 of ABCA4.
The Stargardt's Disease, Type 1 (STGD1) is associated with the loss of function mutations in ABCA4. This gene codes for a retina-specific, ATP-binding cassette (ABC) family transporter, involved in the transport of the key visual cycle intermediate, all-trans-retinaldehyde (atRAL), across the photoreceptor cell membranes. Here, we report the establishment of a patient-specific, iPSC line (LVPEIi008-A), that carries a homozygous nonsense mutation at (c.6088C > T) position, within exon 44 of ABCA4. The patient-specific skin fibroblasts were reprogrammed using episomal plasmids and the stably expanding iPSC line expressed the key stemness and pluripotency markers, maintained its chromosomal integrity and tested negative for mycoplasma.
Topics: Induced Pluripotent Stem Cells; ATP-Binding Cassette Transporters; Stargardt Disease; Humans; Codon, Nonsense; Exons; Homozygote; Cell Line; Macular Degeneration
PubMed: 38870564
DOI: 10.1016/j.scr.2024.103458 -
Journal of Global Health Jun 2024Asia accounts for more than half of the world's population and carries a substantial proportion of the global burden of blindness and vision impairment. Characterising...
BACKGROUND
Asia accounts for more than half of the world's population and carries a substantial proportion of the global burden of blindness and vision impairment. Characterising this burden, as well as its causes and determinants, could help with devising targeted interventions for reducing the occurrence of blindness and visual impairment.
METHODS
Using the Global Burden of Disease Study 2019 database, we retrieved data on the number of disability-adjusted life years (DALYs); crude and age-standardised rates; and the prevalence (with 95% uncertainty intervals (95%UIs)) of blindness and vision loss due to six causes (age-related macular degeneration, cataracts, glaucoma, near-vision impairment, refractive error, and other vision loss) for Asian countries for the period between 1990 and 2019. We defined DALYs as the sum of the years lost due to disability and years of life lost, and calculated age-standardised figures for the number of DALYs and prevalence by adjusting for population size and age structure. We then evaluated the time trend of the disease burden and conducted subgroup analyses by gender, age, geographic locations, and socio-demographic index (SDI).
RESULTS
In 2019, the DALYs and prevalence of blindness and vision loss had risen by 90.1% and 116% compared with 1990, reaching 15.84 million DALYs (95% UI = 15.83, 15.85) and 506.71 million cases (95% UI = 506.68, 506.74). Meanwhile, the age-standardised rate of DALYs decreased from 1990 to 2019. Cataracts, refractive error, and near vision impairment were the three most common causes. South Asia had the heaviest regional disease burden (age-standardised rate of DALYs = 517 per 100 000 population; 95% UI = 512, 521). Moreover, the burden due to cataracts ranked high in most Asian populations. Being a woman; being older; and having a lower national SDI were factors associated with a greater vision loss burden.
CONCLUSIONS
The burden due to vision loss remains high in Asian populations. Cataracts, refractive error, and near vision loss were the primary causes of blindness and vision loss. Greater investment in ocular disease prevention and care by countries with lower socioeconomic status is needed, as well as specific strategies targeting cataract management, women and the elderly.
Topics: Humans; Blindness; Global Burden of Disease; Female; Male; Aged; Middle Aged; Asia; Disability-Adjusted Life Years; Adult; Aged, 80 and over; Prevalence; Young Adult; Adolescent; Child; Child, Preschool; Infant; Cataract; Vision, Low; Refractive Errors
PubMed: 38867671
DOI: 10.7189/jogh.14.04100 -
Photodiagnosis and Photodynamic Therapy Jun 2024To analyze the characteristics of macular retinal vessel density and thickness in children with myopia.
PURPOSE
To analyze the characteristics of macular retinal vessel density and thickness in children with myopia.
METHODS
A cross-sectional study was conducted. A total of 228 children aged 4-16 years who visited the Ineye Hospital of Chengdu University of Traditional Chinese Medicine from September 2022 to November 2023 were included. Those with -0.5D < spherical equivalent (SE) < +2.0D were included in the non-myopia group (150 eyes), those with -3.0D < SE ≤ -0.5D were included in the low myopia group (246 eyes), and those with SE ≤ -3.0D were included in the moderate-to-high myopia group (60 eyes). All subjects underwent cycloplegic refraction, IOLmaster500, and Wide-field SS-OCTA (to exclude some peripheral retinal degeneration). Multiple linear regression analysis was used to analyze the correlation between macular ETDRS subfield of full retinal thickness (FRT), outer, inner retinal thickness (ORT, IRT), retinal vessel density (VD), deep and superficial retinal vessel density (DVD, SVD), and SE, axial length (AL).
RESULTS
There were statistically significant differences (P < 0.05) in FRT in the central fovea (1 mm diameter)and perifovea (Diameter 3 to 6 mm) among the non-myopia group, low myopia group, and moderate-to-high myopia group. The three groups also showed statistically significant differences (P < 0.05) in VD in the central fovea and parafovea with a diameter of 1 to 3 mm (except the lower part). In multiple linear regression analysis adjusted for gender and age, SE and AL were found to be correlated with FRT in all ETDRS regions (except the central fovea) (P < 0.01), and SE and AL were correlated with IRT in the central fovea and perifovea, respectively (β range -2.302 to 1.652; P < 0.05). SE and AL were also correlated with ORT in the parafovea and perifovea, respectively (β range -4.371 to -2.344; P < 0.05). AL was negatively correlated with VD in the central fovea and parafovea (except the inferior region) (P < 0.05), as well as with DVD in all ETDRS regions (β range -1.314 to -1.031; P < 0.05). AL was only negatively correlated with SVD in the parafoveal nasal region (β = -0.633, P < 0.05). Additionally, the correlation between AL and DVD, ORT was higher than that with SVD, IRT.
CONCLUSION
The more severe the myopia, the longer the AL, the thinner the FRT in the perifovea, and the lower the VD in both the fovea and parafovea in children. In addition, DVD and ORT were more significantly correlated with AL, suggesting that they may be more closely related to the growth of AL.
PubMed: 38866069
DOI: 10.1016/j.pdpdt.2024.104240 -
Proceedings of the National Academy of... Jun 2024Loss of mitochondrial electron transport complex (ETC) function in the retinal pigment epithelium (RPE) in vivo results in RPE dedifferentiation and progressive...
Loss of mitochondrial electron transport complex (ETC) function in the retinal pigment epithelium (RPE) in vivo results in RPE dedifferentiation and progressive photoreceptor degeneration, and has been implicated in the pathogenesis of age-related macular degeneration. Xenogenic expression of alternative oxidases in mammalian cells and tissues mitigates phenotypes arising from some mitochondrial electron transport defects, but can exacerbate others. We expressed an alternative oxidase from (AOX) in ETC-deficient murine RPE in vivo to assess the retinal consequences of stimulating coenzyme Q oxidation and respiration without ATP generation. RPE-restricted expression of AOX in this context is surprisingly beneficial. This focused intervention mitigates RPE mTORC1 activation, dedifferentiation, hypertrophy, stress marker expression, pseudohypoxia, and aerobic glycolysis. These RPE cell autonomous changes are accompanied by increased glucose delivery to photoreceptors with attendant improvements in photoreceptor structure and function. RPE-restricted AOX expression normalizes accumulated levels of succinate and 2-hydroxyglutarate in ETC-deficient RPE, and counteracts deficiencies in numerous neural retinal metabolites. These features can be attributed to the activation of mitochondrial inner membrane flavoproteins such as succinate dehydrogenase and proline dehydrogenase, and alleviation of inhibition of 2-oxyglutarate-dependent dioxygenases such as prolyl hydroxylases and epigenetic modifiers. Our work underscores the importance to outer retinal health of coenzyme Q oxidation in the RPE and identifies a metabolic network critical for photoreceptor survival in the context of RPE mitochondrial dysfunction.
Topics: Animals; Mitochondria; Mice; Oxidoreductases; Retinal Pigment Epithelium; Plant Proteins; Mitochondrial Proteins; Ciona intestinalis; Ubiquinone; Retinal Degeneration; Photoreceptor Cells, Vertebrate
PubMed: 38865272
DOI: 10.1073/pnas.2402384121 -
BMC Ophthalmology Jun 2024Peripapillary hyperreflective ovoid mass-like structures (PHOMS) are newly characterized lesions wedged around the optic discs, which used to be misdiagnosed. Better...
BACKGROUND
Peripapillary hyperreflective ovoid mass-like structures (PHOMS) are newly characterized lesions wedged around the optic discs, which used to be misdiagnosed. Better understanding and identifying PHOMS are important for monitoring the condition of optic nerve.
CASE PRESENTATION
A young female presented to the ophthalmic clinic with blurred vision of both eyes. Protrusions resembling "C-shaped donut" were found circling the optic discs bilaterally. These lesions were homogenous hyperreflective on OCT, while they were also hypoautofluorescent and hypoechogenic. Meanwhile, cystoid macular edema (CME) was also identified in both eyes. The patient was then diagnosed as PHOMS with CME. A short-term glucocorticoids therapy was prescribed systemically. The logMAR best-corrected visual acuity (BCVA) of both eyes reached 0.0 in 4 months with recovery of CME, while the PHOMS remained.
CONCLUSIONS
There is currently no report on PHOMS with CME. More attentions should be paid to PHOMS, for they are potential biomarkers for axoplasmic stasis involved in different diseases of the optic nerve.
Topics: Humans; Macular Edema; Female; Tomography, Optical Coherence; Visual Acuity; Optic Disk; Adult; Glucocorticoids; Fluorescein Angiography; Optic Nerve Diseases
PubMed: 38862962
DOI: 10.1186/s12886-024-03509-3