Exploring the role of granzyme B in subretinal fibrosis of age-related macular degeneration.

Age-related macular degeneration (AMD), a prevalent and progressive degenerative disease of the macula, is the leading cause of blindness in elderly individuals in developed countries. The advanced stages include neovascular AMD (nAMD), characterized by choroidal neovascularization (CNV), leading to subretinal fibrosis and permanent vision loss. Despite the efficacy of anti-vascular endothelial growth factor (VEGF) therapy in stabilizing or improving vision in nAMD, the development of subretinal fibrosis following CNV remains a significant concern. In this review, we explore multifaceted aspects of subretinal fibrosis in nAMD, focusing on its clinical manifestations, risk factors, and underlying pathophysiology. We also outline the potential sources of myofibroblast precursors and inflammatory mechanisms underlying their recruitment and transdifferentiation. Special attention is given to the potential role of mast cells in CNV and subretinal fibrosis, with a focus on putative mast cell mediators, tryptase and granzyme B. We summarize our findings on the role of GzmB in CNV and speculate how GzmB may be involved in the pathological transition from CNV to subretinal fibrosis in nAMD. Finally, we discuss the advantages and drawbacks of animal models of subretinal fibrosis and pinpoint potential therapeutic targets for subretinal fibrosis.

[Identification of TCTN1 gene variants in a fetus with Joubert syndrome 13].

OBJECTIVE: To explore the clinical characteristics and genetic basis for a fetus with Joubert syndrome. METHODS: A pregnant woman who had visited Suzhou Municipal Hospital on February 26, 2021 was selected as the study subject. The fetus and her parents were subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing. cDNA analysis of her father and RNA sequencing of her sister were also carried out. RESULTS: The fetus was found to harbor compound heterozygous variants of the TCTN1 gene, namely c.624G>A and c.96dupA (p.Glu33Argfs*49), which were inherited from her father and mother, respectively. Her sister also carried the paternal c.624G>A variant, and mRNA transcripts with the c.624G>A variant of the TCTN1 gene were not detected by cDNA analysis of her father and RNA sequencing of her sister. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.624G>A and c.96dupA variants were both classified as likely pathogenic (PVS1+PM2_Supporting). CONCLUSION: The compound heterozygous variants of the TCTN1 gene probably underlay the pathogenesis in this fetus. Above finding has also expanded the mutational spectrum of the TCTN1 gene.

The people behind the papers - Kevin Emmerich and Jeff Mumm.

Retinal regeneration has been mostly studied after widespread tissue injury, but it is not well understood how the retina regenerates at the cellular level following loss of specific cell types. In a new study, Jeff Mumm and colleagues selectively ablate retinal ganglion cells in zebrafish and find that the retina elicits different genetic responses in a context-dependent manner to replace lost cells. To find out more about the story behind the paper, we caught up with first author Kevin Emmerich and corresponding author Jeff Mumm, Associate Professor in Ophthalmology at Johns Hopkins University.

Electroretinographic Evaluations of Eyes With Endophthalmitis.

Purpose: To determine the physiological status of the retina of eyes with endophthalmitis by examining the electroretinograms (ERGs) recorded with a portable recording system and to determine whether the pretreatment ERG findings were correlated with the best-corrected visual acuity (BCVA) after the treatment. Methods: We examined the medical records of 118 eyes of 108 patients who were diagnosed and treated for infectious endophthalmitis at Saitama Medical University Hospital, Japan, between January 2015 to November 2022. Of these, we studied the 25 eyes of 21 patients who had been evaluated by electroretinography. In bilateral cases, one eye was analyzed. The eyes were classified into those with postoperative endophthalmitis (group S, n = 12) and those with endogenous endophthalmitis (group E, n = 9). Photopic and flicker ERGs were recorded with the RETeval system. The pretreatment clinical factors studied were the ERG components that might be correlated with the post-treatment BCVA. Results: Eyes in Group E with larger amplitude flicker ERGs (P = 0.0053, ρ = -0.8333) had better BCVA after treatment. In Group S, eyes with larger amplitude flicker ERGs (P = 0.0086, ρ = -0.7173), photopic a-waves (P = 0.0323, ρ = 0.6177), and photopic b-waves (P = 0.0055, ρ = -0.7443) had better BCVA after treatment. Conclusions: Simple and rapid ERG evaluations under light-adapted condition are helpful in evaluating the pretreatment retinal function and to determine the visual prognosis in eyes with endophthalmitis. Translational Relevance: Simple and non-time-consuming ERG evaluations are helpful in evaluating the retinal function in eyes with endophthalmitis and predicting the visual prognosis.

VMseg: Using spatial variance to automatically segment retinal non-perfusion on OCT-angiography.

BACKGROUND AND OBJECTIVES: To develop and test VMseg, a new image processing algorithm performing automatic segmentation of retinal non-perfusion in widefield OCT-Angiography images, in order to estimate the non-perfusion index in diabetic patients. METHODS: We included diabetic patients with severe non-proliferative or proliferative diabetic retinopathy. We acquired images using the PlexElite 9000 OCT-A device with a photomontage of 5 images of size 12 x 12 mm. We then developed VMseg, a Python algorithm for non-perfusion detection, which binarizes a variance map calculated through convolution and morphological operations. We used 70% of our data set (development set) to fine-tune the algorithm parameters (convolution and morphological parameters, binarization thresholds) and evaluated the algorithm performance on the remaining 30% (test set). The obtained automatic segmentations were compared to a ground truth corresponding to manual segmentation from a retina expert and the inference processing time was estimated. RESULTS: We included 51 eyes of 30 patients (27 severe non-proliferative, 24 proliferative diabetic retinopathy). Using the optimal parameters found on the development set to tune the algorithm, the mean dice for the test set was 0.683 (sd = 0.175). We found a higher dice coefficient for images with a higher area of retinal non-perfusion (rs = 0.722, p < 10-4). There was a strong correlation (rs = 0.877, p < 10-4) between VMseg estimated non-perfusion indexes and indexes estimated using the ground truth segmentation. The Bland-Altman plot revealed that 3 eyes (5.9%) were significantly under-segmented by VMseg. CONCLUSION: We developed VMseg, an automatic algorithm for retinal non-perfusion segmentation on 12 x 12 mm OCT-A widefield photomontages. This simple algorithm was fast at inference time, segmented images in full-resolution and for the OCT-A format, was accurate enough for automatic estimation of retinal non-perfusion index in diabetic patients with diabetic retinopathy.

The effect of long-term hemodialysis on diabetic retinopathy observed by swept-source optical coherence tomography angiography.

BACKGROUND: Diabetes can cause chronic microvascular complications such as diabetic retinopathy (DR) and diabetic nephropathy (DN). DR and DN can lead to or exacerbate diabetic macular edema (DME). Hemodialysis (HD) is the main treatment method for patients with end-stage kidney disease (ESKD) secondary to DN. PURPOSE: The aim of this prospective cohort study was to determine the immediate effect of single HD session on retinal and choroidal thickness in DR patients with ESKD and the features of DR and the prevalence of DME in these patients who have received long-term HD. METHODS: Eighty-five eyes of 44 DR patients with ESKD who underwent long-term HD were examined by swept-source optical coherence tomography angiography (SS-OCTA). Based on OCTA images, the characteristics of DR and the prevalence of DME in these patients were analyzed. Changes in central retinal thickness (CRT), central retinal volume (CRV), subfoveal choroidal thickness (SFCT) and subfoveal choroidal volume (SFCV) within 30 min before and after single HD session were compared. CRT, CRV, SFCT and SFCV were compared before single HD session and before the next single HD session. RESULTS: There was no significant difference in the average CRT (251.69 ± 39.21 µm vs. 251.46 ± 39.38 µm, P = 0.286) or CRV (0.15 ± 0.62 µm vs. 0.15 ± 0.63 µm, P = 0.324) between before and after single HD session. After single HD session, SFCT (243.11 ± 77.15 µm vs. 219.20 ± 72.84 µm, P < 0.001) and SFCV (0.15 ± 0.10 µm vs. 0.13 ± 0.90 µm, P < 0.001) significantly decreased. There was no statistically significant difference in CRT (251.69 ± 39.21 µm vs. 251.11 ± 38.47 µm, P = 0.206), CRV (0.15 ± 0.62 µm vs. 0.15 ± 0.61 µm, P = 0.154), SFCT (243.11 ± 77.15 µm vs. 245.41 ± 76.23 µm, P = 0.108), or SFCV (0.15 ± 0.10 µm vs. 0.16 ± 0.10 µm, P = 0.174) before HD and before the next single HD session. On en face OCTA images, eighty-five eyes (100%) had retinal nonperfusion areas, foveal avascular zone (FAZ) enlargement, and abnormal retinal microvasculature. Based on cross-sectional OCTA images, retinal neovascularization (RNV) was confirmed in 42 eyes (49.41%), and intraretinal microvascular abnormalities (IRMAs) were detected in 85 eyes (100%). Seventeen eyes (20%) still had DME, all of which were cystoid macular edema (CME). Among eyes with DME, the epiretinal membrane (ERM) was present in 7 eyes (8.24%). CONCLUSIONS: For DR patients with ESKD who have undergone long-term HD, the choroidal thickness still changes significantly before and after single HD session, which may be related to short-term effects such as reduced blood volume and plasma osmotic pressure caused by single HD session. Although macular features seem to have stabilized in DR patients undergoing long-term dialysis, the DR of patients with ESKD should still be given attention.

Evaluation of neuroretina following i.v. or intra-CSF AAV9 gene replacement in mice with MPS IIIA, a childhood dementia.

BACKGROUND: Sanfilippo syndrome (mucopolysaccharidosis type IIIA; MPS IIIA) is a childhood dementia caused by inherited mutations in the sulfamidase gene. At present, there is no treatment and children with classical disease generally die in their late teens. Intravenous or intra-cerebrospinal fluid (CSF) injection of AAV9-gene replacement is being examined in human clinical trials; evaluation of the impact on brain disease is an intense focus; however, MPS IIIA patients also experience profound, progressive photoreceptor loss, leading to night blindness. AIM: To compare the relative efficacy of the two therapeutic approaches on retinal degeneration in MPS IIIA mice. METHODS: Neonatal mice received i.v. or intra-CSF AAV9-sulfamidase or vehicle and after 20 weeks, biochemical and histological evaluation of neuroretina integrity was carried out. RESULTS: Both treatments improved central retinal thickness; however, in peripheral retina, outer nuclear layer thickness and photoreceptor cell length were only significantly improved by i.v. gene replacement. Further, normalization of endo-lysosomal compartment size and microglial morphology was only observed following intravenous gene delivery. CONCLUSIONS: Confirmatory studies are needed in adult mice; however, these data indicate that i.v. AAV9-sulfamidase infusion leads to superior outcomes in neuroretina, and cerebrospinal fluid-delivered AAV9 may need to be supplemented with another therapeutic approach for optimal patient quality of life.

Multimodal Retinal Imaging Classification for Parkinson's Disease Using a Convolutional Neural Network.

Purpose: Changes in retinal structure and microvasculature are connected to parallel changes in the brain. Two recent studies described machine learning algorithms trained on retinal images and quantitative data that identified Alzheimer's dementia and mild cognitive impairment with high accuracy. Prior studies also demonstrated retinal differences in individuals with PD. Herein, we developed a convolutional neural network (CNN) to classify multimodal retinal imaging from either a Parkinson's disease (PD) or control group. Methods: We trained a CNN to receive retinal image inputs of optical coherence tomography (OCT) ganglion cell-inner plexiform layer (GC-IPL) thickness color maps, OCT angiography 6 × 6-mm en face macular images of the superficial capillary plexus, and ultra-widefield (UWF) fundus color and autofluorescence photographs to classify the retinal imaging as PD or control. The model consists of a shared pretrained VGG19 feature extractor and image-specific feature transformations which converge to a single output. Model results were assessed using receiver operating characteristic (ROC) curves and bootstrapped 95% confidence intervals for area under the ROC curve (AUC) values. Results: In total, 371 eyes of 249 control subjects and 75 eyes of 52 PD subjects were used for training, validation, and testing. Our best CNN variant achieved an AUC of 0.918. UWF color photographs were the most effective imaging input, and GC-IPL thickness maps were the least contributory. Conclusions: Using retinal images, our pilot CNN was able to identify individuals with PD and serves as a proof of concept to spur the collection of larger imaging datasets needed for clinical-grade algorithms. Translational Relevance: Developing machine learning models for automated detection of Parkinson's disease from retinal imaging could lead to earlier and more widespread diagnoses.

Physics-informed deep generative learning for quantitative assessment of the retina.

Disruption of retinal vasculature is linked to various diseases, including diabetic retinopathy and macular degeneration, leading to vision loss. We present here a novel algorithmic approach that generates highly realistic digital models of human retinal blood vessels, based on established biophysical principles, including fully-connected arterial and venous trees with a single inlet and outlet. This approach, using physics-informed generative adversarial networks (PI-GAN), enables the segmentation and reconstruction of blood vessel networks with no human input and which out-performs human labelling. Segmentation of DRIVE and STARE retina photograph datasets provided near state-of-the-art vessel segmentation, with training on only a small (n = 100) simulated dataset. Our findings highlight the potential of PI-GAN for accurate retinal vasculature characterization, with implications for improving early disease detection, monitoring disease progression, and improving patient care.

Age-related retinal degeneration resulting from the deletion of Shp2 tyrosine phosphatase in photoreceptor neurons.

Shp2, a critical SH2-domain-containing tyrosine phosphatase, is essential for cellular regulation and implicated in metabolic disruptions, obesity, diabetes, Noonan syndrome, LEOPARD syndrome, and cancers. This study focuses on Shp2 in rod photoreceptor cells, revealing its enrichment, particularly in rods. Deletion of Shp2 in rods leads to age-dependent photoreceptor degeneration. Shp2 targets occludin (OCLN), a tight junction protein, and its deletion reduces OCLN expression in the retina and retinal pigment epithelium (RPE). The isolation of actively translating mRNAs from rods lacking Shp2, followed by RNA sequencing, reveals alterations in cell cycle regulation. Additionally, altered retinal metabolism is observed in retinal cells lacking Shp2. Our studies indicate that Shp2 is crucial for maintaining the structure and function of photoreceptors.

Preservation of retinal structure and function in two mouse models of inherited retinal degeneration by ONL1204, an inhibitor of the Fas receptor.

Due to the large number of genes and mutations that result in inherited retinal degenerations (IRD), there has been a paucity of therapeutic options for these patients. There is a large unmet need for therapeutic approaches targeting shared pathophysiologic pathways in a mutation-independent manner. The Fas receptor is a major activator and regulator of retinal cell death and inflammation in a variety of ocular diseases. We previously reported the activation of Fas-mediated photoreceptor (PR) cell death in two different IRD mouse models, rd10 and P23H, and demonstrated the protective effect of genetic Fas inhibition. The purpose of this study was to examine the effects of pharmacologic inhibition of Fas in these two models by intravitreal injection with a small peptide inhibitor of the Fas receptor, ONL1204. A single intravitreal injection of ONL1204 was given to one eye of rd10 mice at P14. Two intravitreal injections of ONL1204 were given to the P23H mice, once at P14 and again at 2-months of age. The fellow eyes were injected with vehicle alone. Fas activation, rate of PR cell death, retinal function, and the activation of immune cells in the retina were evaluated. In both rd10 and P23H mice, ONL1204 treatment resulted in decreased number of TUNEL (+) PRs, decreased caspase 8 activity, enhanced photoreceptor cell counts, and improved visual function compared with vehicle treated fellow eyes. Treatment with ONL1204 also reduced immune cell activation in the retinas of both rd10 and P23H mice. The protective effect of pharmacologic inhibition of Fas by ONL1204 in two distinct mouse models of retinal degeneration suggests that targeting this common pathophysiologic mechanism of cell death and inflammation represents a potential therapeutic approach to preserve the retina in patients with IRD, regardless of the genetic underpinning.

Single cell dual-omic atlas of the human developing retina.

The development of the retina is under tight temporal and spatial control. To gain insights into the molecular basis of this process, we generate a single-nuclei dual-omic atlas of the human developing retina with approximately 220,000 nuclei from 14 human embryos and fetuses aged between 8 and 23-weeks post-conception with matched macular and peripheral tissues. This atlas captures all major cell classes in the retina, along with a large proportion of progenitors and cell-type-specific precursors. Cell trajectory analysis reveals a transition from continuous progression in early progenitors to a hierarchical development during the later stages of cell type specification. Both known and unrecorded candidate transcription factors, along with gene regulatory networks that drive the transitions of various cell fates, are identified. Comparisons between the macular and peripheral retinae indicate a largely consistent yet distinct developmental pattern. This atlas offers unparalleled resolution into the transcriptional and chromatin accessibility landscapes during development, providing an invaluable resource for deeper insights into retinal development and associated diseases.

Rapid and efficient generation of mature retinal organoids derived from human pluripotent stem cells via optimized pharmacological modulation of Sonic hedgehog, activin A, and retinoic acid signal transduction.

Human retinal organoids have become indispensable tools for retinal disease modeling and drug screening. Despite its versatile applications, the long timeframe for their differentiation and maturation limits the throughput of such research. Here, we successfully shortened this timeframe by accelerating human retinal organoid development using unique pharmacological approaches. Our method comprised three key steps: 1) a modified self-formed ectodermal autonomous multizone (SEAM) method, including dual SMAD inhibition and bone morphogenetic protein 4 treatment, for initial neural retinal induction; 2) the concurrent use of a Sonic hedgehog agonist SAG, activin A, and all-trans retinoic acid for rapid retinal cell specification; and 3) switching to SAG treatment alone for robust retinal maturation and lamination. The generated retinal organoids preserved typical morphological features of mature retinal organoids, including hair-like surface structures and well-organized outer layers. These features were substantiated by the spatial immunostaining patterns of several retinal cell markers, including rhodopsin and L/M opsin expression in the outermost layer, which was accompanied by reduced ectopic cone photoreceptor generation. Importantly, our method required only 90 days for retinal organoid maturation, which is approximately two-thirds the time necessary for other conventional methods. These results indicate that thoroughly optimized pharmacological interventions play a pivotal role in rapid and precise photoreceptor development during human retinal organoid differentiation and maturation. Thus, our present method may expedite human retinal organoid research, eventually contributing to the development of better treatment options for various degenerative retinal diseases.

Influence of Carotid Artery Stenting on the Retina and Choroid.

Purpose: The effect of carotid artery stenting in patients with unilateral carotid artery stenosis on the retina and choroid was evaluated using swept-source optical coherence tomography angiography (SS-OCTA). Methods: SS-OCTA examination was conducted before stenting and 4 days and 3 months after stenting. The retinal nerve fiber layer, ganglion cell-inner plexiform layer (GCIPL), inner nuclear layer, superficial vascular complex (SVC), deep vascular complex (DVC), choroidal vascular volume (CVV), and choroidal vascular index were measured. Repeated-measures analysis of variance was performed to assess the impact of carotid artery stenting on optical coherence tomography angiography (OCTA) metrics. Results: At baseline, 303 eyes from 160 patients (61.82 ± 9.98 years; 85.29% males) were enrolled. SVC and DVC densities and CVV were lower in ipsilateral eyes (stenosed side) compared to contralateral eyes (all P < 0.05). Four days after stenting, a significant increase was seen in SVC density in ipsilateral eyes (P < 0.05) while a significant increase was seen in CVV in ipsilateral eyes and contralateral eyes (both P < 0.05). Three months after stenting (63 patients with 114 eyes), a significant decrease was seen in the GCIPL thickness of ipsilateral and contralateral eyes (all P < 0.001). Conclusions: Short term after carotid artery stenting, ipsilateral eyes showed a rapid and significant increase in SVC density and CVV. Translational Relevance: Optical coherence tomography (OCT)/OCTA measurements may have the potential to detect retinal and choroidal changes after stenting. Future research on the long-term effect of stenting on the retina and choroid will be guided by these findings.

Optimization of an Ischemic Retinopathy Mouse Model and the Consequences of Hypoxia in a Time-Dependent Manner.

The retina is one of the highest metabolically active tissues with a high oxygen consumption, so insufficient blood supply leads to visual impairment. The incidence of related conditions is increasing; however, no effective treatment without side effects is available. Furthermore, the pathomechanism of these diseases is not fully understood. Our aim was to develop an optimal ischemic retinopathy mouse model to investigate the retinal damage in a time-dependent manner. Retinal ischemia was induced by bilateral common carotid artery occlusion (BCCAO) for 10, 13, 15 or 20 min, or by right permanent unilateral common carotid artery occlusion (UCCAO). Optical coherence tomography was used to follow the changes in retinal thickness 3, 7, 14, 21 and 28 days after surgery. The number of ganglion cells was evaluated in the central and peripheral regions on whole-mount retina preparations. Expression of glial fibrillary acidic protein (GFAP) was analyzed with immunohistochemistry and Western blot. Retinal degeneration and ganglion cell loss was observed in multiple groups. Our results suggest that the 20 min BCCAO is a good model to investigate the consequences of ischemia and reperfusion in the retina in a time-dependent manner, while the UCCAO causes more severe damage in a short time, so it can be used for testing new drugs.

Development of Non-Invasive miRNA Markers for Assessing the Quality of Human Induced Pluripotent Stem Cell-Derived Retinal Organoids.

Human retinal organoids (ROs) have emerged as valuable tools for studying retinal development, modeling human retinal diseases, and screening drugs. However, their application is limited primarily due to time-intensive generation, high costs, and low reproducibility. Quality assessment of RO differentiation is crucial for their application in research. However, traditional methods such as morphological evaluation and immunohistochemical analysis have limitations due to their lack of precision and invasiveness, respectively. This study aims to identify non-invasive biomarkers for RO differentiation quality using exosomal microRNAs (miRNAs), which are known to reflect cell-specific functions and development in the retina. We differentiated ROs from human induced pluripotent stem cells (hiPSCs) and classified them into 'superior' and 'inferior' groups based on morphological and immunohistochemical criteria. Exosomes from the conditioned media were isolated and analyzed for miRNA content. Our findings revealed distinct miRNA profiles between superior and inferior ROs, with superior ROs exhibiting higher miRNA diversity and specifically up- or down-regulated miRNAs. Gene ontology and pathway enrichment analyses indicated that the target genes of these miRNAs are involved in neuron proliferation and differentiation. The study suggests the potential of exosomal hsa-miR-654-3p and hsa-miR-451a as non-invasive biomarkers for real-time monitoring of RO quality, facilitating the development of standardized, efficient, and cost-effective culture methods.

Amelioration of Photoreceptor Degeneration by Intravitreal Transplantation of Retinal Progenitor Cells in Rats.

Photoreceptor degeneration is a major cause of untreatable blindness worldwide and has recently been targeted by emerging technologies, including cell- and gene-based therapies. Cell types of neural lineage have shown promise for replacing either photoreceptors or retinal pigment epithelial cells following delivery to the subretinal space, while cells of bone marrow lineage have been tested for retinal trophic effects following delivery to the vitreous cavity. Here we explore an alternate approach in which cells from the immature neural retinal are delivered to the vitreous cavity with the goal of providing trophic support for degenerating photoreceptors. Rat and human retinal progenitor cells were transplanted to the vitreous of rats with a well-studied photoreceptor dystrophy, resulting in substantial anatomical preservation and functional rescue of vision. This work provides scientific proof-of-principle for a novel therapeutic approach to photoreceptor degeneration that is currently being evaluated in clinical trials.

Early Developmental Characteristics and Features of a Three-Dimensional Retinal Organoid Model of X-Linked Juvenile Retinoschisis.

X-linked juvenile retinoschisis (XLRS) is a hereditary retinal degeneration affecting young males caused by mutations in the retinoschisin (RS1) gene. We generated human induced pluripotent stem cells (hiPSCs) from XLRS patients and established three-dimensional retinal organoids (ROs) for disease investigation. This disease model recapitulates the characteristics of XLRS, exhibiting defects in RS1 protein production and photoreceptor cell development. XLRS ROs also revealed dysregulation of Na/K-ATPase due to RS1 deficiency and increased ERK signaling pathway activity. Transcriptomic analyses of XLRS ROs showed decreased expression of retinal cells, particularly photoreceptor cells. Furthermore, relevant recovery of the XLRS phenotype was observed when co-cultured with control ROs derived from healthy subject during the early stages of differentiation. In conclusion, our in vitro XLRS RO model presents a valuable tool for elucidating the pathophysiological mechanisms underlying XLRS, offering insights into disease progression. Additionally, this model serves as a robust platform for the development and optimization of targeted therapeutic strategies, potentially improving treatment outcomes for patients with XLRS.

Age-Related Retinal Layer Thickness Changes Measured by OCT in APPNL-F/NL-F Mice: Implications for Alzheimer's Disease.

In Alzheimer's disease (AD), transgenic mouse models have established links between abnormalities in the retina and those in the brain. APPNL-F/NL-F is a murine, humanized AD model that replicates several pathological features observed in patients with AD. Research has focused on obtaining quantitative parameters from optical coherence tomography (OCT) in AD. The aim of this study was to analyze, in a transversal case-control study using manual retinal segmentation via SD-OCT, the changes occurring in the retinal layers of the APPNL/F-NF/L AD model in comparison to C57BL/6J mice (WT) at 6, 9, 12, 15, 17, and 20 months of age. The analysis focused on retinal thickness in RNFL-GCL, IPL, INL, OPL, and ONL based on the Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. Both APPNL-F/NL-F-model and WT animals exhibited thickness changes at the time points studied. While WT showed significant changes in INL, OPL, and ONL, the AD model showed changes in all retinal layers analyzed. The APPNL-F/NL-F displayed significant thickness variations in the analyzed layers except for the IPL compared to related WT. These thickness changes closely resembled those found in humans during preclinical stages, as well as during mild and moderate AD stages, making this AD model behave more similarly to the disease in humans.