Retinal Progression Biomarkers of Early and Intermediate Age-Related Macular Degeneration

Flores, Rita; Carneiro, Ângela; Tenreiro, Sandra; Seabra, Miguel C.

doi:10.3390/life12010036

Cited by 18 publications

(21 citation statements)

References 72 publications

(129 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While risk factors for AMD have been well defined ( 1 , 11 , 45 , 46 ), they are also multifactorial in nature, creating a level of complexity in both disease diagnosis and intervention/treatment strategies. Further complicating diagnostic accuracies, early pathological signs, including small yellow lipid-filled deposits under the retina called drusen, as well as pigmentary abnormalities, can only be used to indicate the potential risk of AMD development, as they can also be found within the healthy aging population ( 1 , 6 , 12 , 47 , 48 ). Therefore, for those at risk, currently the only intervention strategy to combat AMD progression is dietary supplementation of AREDS2 formulation multivitamins, however this remains only efficacious in slowing the progression from intermediate to late-stage AMD ( 49 , 50 ).…”

Section: Discussionmentioning

confidence: 99%

Short exposure to photo-oxidative damage triggers molecular signals indicative of early retinal degeneration

et al. 2023

View full text Add to dashboard Cite

IntroductionAge-related macular degeneration (AMD) is the leading cause of blindness in the developed world, currently affecting over 350 billion people globally. For the most prevalent late-stage form of this disease, atrophic AMD, there are no available prevention strategies or treatments, in part due to inherent difficulties in early-stage diagnosis. Photo-oxidative damage is a well-established model for studying inflammatory and cell death features that occur in late-stage atrophic AMD, however to date has not been investigated as a potential model for studying early features of disease onset. Therefore, in this study we aimed to determine if short exposure to photo-oxidative damage could be used to induce early retinal molecular changes and advance this as a potential model for studying early-stage AMD.MethodsC57BL/6J mice were exposed to 1, 3, 6, 12, or 24h photo-oxidative damage (PD) using 100k lux bright white light. Mice were compared to dim-reared (DR) healthy controls as well as mice which had undergone long periods of photo-oxidative damage (3d and 5d-PD) as known timepoints for inducing late-stage retinal degeneration pathologies. Cell death and retinal inflammation were measured using immunohistochemistry and qRT-PCR. To identify retinal molecular changes, retinal lysates were sent for RNA sequencing, following which bioinformatics analyses including differential expression and pathway analyses were performed. Finally, to investigate modulations in gene regulation as a consequence of degeneration, microRNA (miRNA) expression patterns were quantified using qRT-PCR and visualized using in situ hybridization.ResultsShort exposure to photo-oxidative damage (1-24h-PD) induced early molecular changes in the retina, with progressive downregulation of homeostatic pathways including metabolism, transport and phototransduction observed across this time-course. Inflammatory pathway upregulation was observed from 3h-PD, preceding observable levels of microglia/macrophage activation which was noted from 6h-PD, as well as significant photoreceptor row loss from 24h-PD. Further rapid and dynamic movement of inflammatory regulator miRNA, miR-124-3p and miR-155-5p, was visualized in the retina in response to degeneration.ConclusionThese results support the use of short exposure to photo-oxidative damage as a model of early AMD and suggest that early inflammatory changes in the retina may contribute to pathological features of AMD progression including immune cell activation and photoreceptor cell death. We suggest that early intervention of these inflammatory pathways by targeting miRNA such as miR-124-3p and miR-155-5p or their target genes may prevent progression into late-stage pathology.

show abstract

Section: Discussionmentioning

confidence: 99%

Short exposure to photo-oxidative damage triggers molecular signals indicative of early retinal degeneration

et al. 2023

View full text Add to dashboard Cite

show abstract

“…57 Furthermore, Flores et al identified iRORA as the factor with the higher probability of developing advanced AMD (OR 12.91). 58…”

Section: Atrophic Changesmentioning

confidence: 99%

Optical coherence tomography biomarkers in early and intermediate age‐related macular degeneration: A clinical guide

Vidal‐Oliver,

Montolío‐Marzo,

Gallego‐Pinazo

et al. 2024

Clinical Exper Ophthalmology

View full text Add to dashboard Cite

Advanced forms of age‐related macular degeneration (AMD), characterised by atrophic and neovascular changes, are a leading cause of vision loss in the elderly population worldwide. Prior to the development of advanced AMD, a myriad of risk factors from the early and intermediate stages of AMD have been published in the scientific literature over the last years. The ability to precisely recognise structural and anatomical changes in the ageing macula, altogether with the understanding of the individual risk implications of each one of them is key for an accurate and personalised diagnostic assessment. The present review aims to summarise updated evidence of the relative risk conferred by diverse macular signs, commonly seen on optical coherence tomography, in terms of progression to geographic atrophy or macular neovascularization. This information may also serve as a basis for tailored follow‐up monitoring visits.

show abstract

“…Events that are pathologic take place when external pressures overcome equilibrium. Although anti-angiogenic therapies that block the bioactivity of vascular endothelial growth factor (anti-VEGF) have changed results in nAMD, over 50% of patients still lose their eyesight after therapy [22]. Only the exudative types of the condition are now treatable, and the medication used does so by blocking vascular endothelial growth factor (VEGF).…”

Section: Neovascular Age-related Macular Degenerationmentioning

confidence: 99%

Age-Related Macular Degeneration: Epidemiology, Pathophysiology, Diagnosis, and Treatment

Vyawahare¹,

Shinde²

2022

Cureus

View full text Add to dashboard Cite

The greatest global root of irremediable amaurosis in the venerable is age-related macular degeneration (AMD), a complex eye condition. Clinically, AMD is characterized as being in an early stage to late stage and initially affects the macula, which is the center of the retina (advanced AMD). Age-related cellular and metabolic imbalance are made worse by the creation of excessive amounts of free radical species, which causes mitochondrial malfunction. As a result, in AMD-affected eyes, the deprivation of melanocytes, confection, and eventually atrophy within the retinal tissue are caused by the continued proliferation of oxidative stress caused by systemic antioxidant capacity depletion.In the urbanized, industrialized world, age-related macular degeneration (AMD) is one of the major causes of central vision loss in the older age group. Although several causes and mechanisms for the dysfunction and degeneration of the retinal pigment epithelium (RPE) have previously been identified, the condition's symptoms are still not fully understood. Etiopathogenesis is still not entirely understood. As a result, the RPE fails, allowing an accumulation of aberrant misfolded proteins, due to the loss of anatomical control over oppression, altered homeostasis, dysfunctional lipid homeostasis, and failure of mitochondria.Due to the multitude of interconnected processes, numerous complicated therapy combinations will probably be the best option to deliver the best visual outcomes; these combinations will vary depending on the kind and degree of the condition being treated. Undoubtedly, this will lead to the development of customized preventative medications and, hopefully, the revelation of a potential cure. All the mechanisms involved in the etiology of AMD should be continuously probed to create covariates for other contemporaneous or future problems.

show abstract

Retinal Progression Biomarkers of Early and Intermediate Age-Related Macular Degeneration

Cited by 18 publications

References 72 publications

Short exposure to photo-oxidative damage triggers molecular signals indicative of early retinal degeneration

Short exposure to photo-oxidative damage triggers molecular signals indicative of early retinal degeneration

Optical coherence tomography biomarkers in early and intermediate age‐related macular degeneration: A clinical guide

Age-Related Macular Degeneration: Epidemiology, Pathophysiology, Diagnosis, and Treatment

Contact Info

Product

Resources

About