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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 31764

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Special Issue Editors

Dr. Ana Isabel Ramirez Sebastián

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Guest Editor

1. Instituto de Investigaciones Oftalmológicas Ramón Castroviejo, Universidad Complutense de Madrid (UCM), Madrid, Spain
2. Departamento de Oftalmología y ORL, Facultad de Óptica y Optometría, Universidad Complutense de Madrid, Madrid, Spain
Interests: retina; glaucoma; microglía; astroglia; neurodegeneration

Dr. José A. Fernández-Albarral

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Co-Guest Editor

Instituto de Investigaciones Oftalmológicas Ramón Castroviejo, Universidad Complutense de Madrid, 28040 Madrid, Spain
Interests: neurophysioly; central nervous system; neuronal and glial cells; neuroinflammation; therapeutical approaches
Special Issues, Collections and Topics in MDPI journals

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Dear Colleagues,

The retina is one of the main structures of the eye and a fundamental part of the vision process. It is also part of the central nervous system (CNS), as it is an extension of the brain.

As a fundamental structure in the visual process, the retina is involved in several pathologies that affect vision and constitute one of the main causes of blindness in the world, including age-related macular degeneration, diabetic retinopathy, and glaucoma, among others. Therefore, advances in research into the pathogenic mechanisms of these diseases and their treatments could represent a major advance in the control of these retinal pathologies.

As part of the central nervous system, the retina can undergo pathological changes related to neurodegenerative processes such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), among others. Thanks to its accessibility and the development of non-invasive imaging techniques, the retina is now considered a biomarker for studying these neurodegenerative pathologies. Therefore, the study of the involvement of the retina in neurodegenerative pathologies, as well as the monitoring, through the retina, of their progression and possible treatments, could represent important advances in the future diagnosis and therapy of these neurodegenerative pathologies.

The Special Issue, "Advanced Researches in Retina", aims to provide a research platform for the collection of the latest original and review articles covering the pathogenic mechanisms of diverse retinal pathologies, innovative diagnostic techniques, and the development of new therapeutic strategies. It also includes articles investigating retinal alterations in neurodegenerative diseases (AD, PD, ALS, among others), the development of new diagnostic techniques using the retina, and the monitoring of new treatments through the retina.

Dr. Ana Isabel Ramirez Sebastián
Dr. José A. Fernández-Albarral
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

glaucoma
age-related macular degeneration
diabetic retinopathy
neurodegenerative diseases
diagnostic techniques
therapeutic strategies

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Advanced Research in Retina 2.0 in International Journal of Molecular Sciences (8 articles)

Published Papers (12 papers)

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Research

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24 pages, 6134 KiB

Open AccessArticle

Oxidative Stress, Inflammatory, Angiogenic, and Apoptotic molecules in Proliferative Diabetic Retinopathy and Diabetic Macular Edema Patients

by Irene Andrés-Blasco, Alex Gallego-Martínez, Ximena Machado, Javier Cruz-Espinosa, Salvatore Di Lauro, Ricardo Casaroli-Marano, Víctor Alegre-Ituarte, José Fernando Arévalo and María Dolores Pinazo-Durán

Int. J. Mol. Sci. 2023, 24(9), 8227; https://doi.org/10.3390/ijms24098227 - 04 May 2023

Cited by 11 | Viewed by 2010

Abstract

The aim of this study is to evaluate molecules involved in oxidative stress (OS), inflammation, angiogenesis, and apoptosis, and discern which of these are more likely to be implicated in proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME) by investigating the correlation between them in the plasma (PLS) and vitreous body (VIT), as well as examining data obtained from ophthalmological examinations. Type 2 diabetic (T2DM) patients with PDR/DME (PDRG/DMEG; n = 112) and non-DM subjects as the surrogate controls (SCG n = 48) were selected according to the inclusion/exclusion criteria and programming for vitrectomy, either due to having PDR/DME or macular hole (MH)/epiretinal membrane (ERM)/rhegmatogenous retinal detachment. Blood samples were collected and processed to determine the glycemic profile, total cholesterol, and C reactive protein, as well as the malondialdehyde (MDA), 4-hydroxynonenal (4HNE), superoxide dismutase (SOD), and catalase (CAT) levels and total antioxidant capacity (TAC). In addition, interleukin 6 (IL6), vascular endothelial growth factor (VEGF), and caspase 3 (CAS3) were assayed. The VITs were collected and processed to measure the expression levels of all the abovementioned molecules. Statistical analyses were conducted using the R Core Team (2022) program, including group comparisons and correlation analyses. Compared with the SCG, our findings support the presence of molecules involved in OS, inflammation, angiogenesis, and apoptosis in the PLS and VIT samples from T2DM. In PLS from PDRG, there was a decrease in the antioxidant load (p < 0.001) and an increase in pro-angiogenic molecules (p < 0.001), but an increase in pro-oxidants (p < 0.001) and a decline in antioxidants (p < 0.001) intravitreally. In PLS from DMEG, pro-oxidants and pro-inflammatory molecules were augmented (p < 0.001) and the antioxidant capacity diminished (p < 0.001), but the pro-oxidants increased (p < 0.001) and antioxidants decreased (p < 0.001) intravitreally. Furthermore, we found a positive correlation between the PLS-CAT and the VIT-SOD levels (rho = 0.5; p < 0.01) in PDRG, and a negative correlation between the PSD-4HNE and the VIT-TAC levels (rho = 0.5; p < 0.01) in DMEG. Integrative data of retinal imaging variables showed a positive correlation between the central subfield foveal thickness (CSFT) and the VIT-SOD levels (rho = 0.5; p < 0.01), and a negative correlation between the CSFT and the VIT-4HNE levels (rho = 0.4; p < 0.01) in PDRG. In DMEG, the CSFT displayed a negative correlation with the VIT-CAT (rho = 0.5; p < 0.01). Exploring the relationship of the abovementioned potential biomarkers between PLS and VIT may help detecting early molecular changes in PDR/DME, which can be used to identify patients at high risk of progression, as well as to monitor therapeutic outcomes in the diabetic retina. Full article

(This article belongs to the Special Issue Advanced Research in Retina)

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19 pages, 3458 KiB

Open AccessArticle

Anti-Inflammatory Effects and Photo- and Neuro-Protective Properties of BIO203, a New Amide Conjugate of Norbixin, in Development for the Treatment of Age-Related Macular Degeneration (AMD)

by Valérie Fontaine, Christine Balducci, Laurence Dinan, Elodie Monteiro, Thinhinane Boumedine, Mylène Fournié, Vincent Nguyen, Louis Guibout, Justine Clatot, Mathilde Latil, Stanislas Veillet, José-Alain Sahel, René Lafont, Pierre J. Dilda and Serge Camelo

Int. J. Mol. Sci. 2023, 24(6), 5296; https://doi.org/10.3390/ijms24065296 - 10 Mar 2023

Cited by 2 | Viewed by 1297

Abstract

9′-cis-norbixin (norbixin/BIO201) protects RPE cells against phototoxicity induced by blue light and N-retinylidene-N-retinylethanolamine (A2E) in vitro and preserves visual functions in animal models of age-related macular degeneration (AMD) in vivo. The purpose of this study was to examine the mode of action and the in vitro and in vivo effects of BIO203, a novel norbixin amide conjugate. Compared to norbixin, BIO203 displays improved stability at all temperatures tested for up to 18 months. In vitro, BIO203 and norbixin share a similar mode of action involving the inhibition of PPARs, NF-κB, and AP-1 transactivations. The two compounds also reduce IL-6, IL-8, and VEGF expression induced by A2E. In vivo, ocular maximal concentration and BIO203 plasma exposure are increased compared to those of norbixin. Moreover, BIO203 administered systemically protects visual functions and retinal structure in albino rats subjected to blue-light illumination and in the retinal degeneration model of Abca4^−/− Rdh8^−/− double knock-out mice following 6 months of oral complementation. In conclusion, we report here that BIO203 and norbixin share similar modes of action and protective effects in vitro and in vivo. BIO203, with its improved pharmacokinetic and stability properties, could be developed for the treatment of retinal degenerative diseases such as AMD. Full article

(This article belongs to the Special Issue Advanced Research in Retina)

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9 pages, 885 KiB

Open AccessArticle

MicroRNA Expression in Subretinal Fluid in Eyes Affected by Rhegmatogenous Retinal Detachment

by Paolo Carpineto, Ester Sara Di Filippo, Agbeanda Aharrh Gnama, Danilo Bondi, Carla Iafigliola, Arturo Maria Licata and Stefania Fulle

Int. J. Mol. Sci. 2023, 24(3), 3032; https://doi.org/10.3390/ijms24033032 - 03 Feb 2023

Cited by 2 | Viewed by 1140

Abstract

Proliferative vitreoretinopathy (PVR) is an abnormal intraocular scarring process that can complicate cases of rhegmatogenous retinal detachment (RRD). Although previous studies have examined the relevance of microRNAs (miRNAs) in ophthalmic diseases, only a few studies have evaluated the expression profiles of microRNAs in subretinal fluid. We hypothesized that the expression profiles of specific miRNAs may change in response to RRD, in the subretinal fluid that is directly in contact with photoreceptors and the retinal pigment epithelium (RPE). We looked for a potential correlation between the expression of specific miRNAs in eyes with RRD and known clinical risk factors of PVR. A total of 24 patients (59 ± 11 years) who underwent scleral buckling procedure were enrolled in this prospective study. Twenty-four undiluted subretinal fluid samples were collected, RNA was isolated and qRT-PCR was performed to analyze the expression of 12 miRNAs. We found the existence of a positive association between the expression of miR-21 (p = 0.017, r = 0.515) and miR-34 (p = 0.030, r = 0.624) and the duration of symptoms related to retinal detachment. Moreover, the expression of miR-146a tended to decrease in patients who developed PVR. Subretinal fluid constitutes an intriguing biological matrix to evaluate the role of miRNAs leading to the development of PVR. Full article

(This article belongs to the Special Issue Advanced Research in Retina)

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19 pages, 3911 KiB

Open AccessArticle

Retinal Tissue Shows Glial Changes in a Dravet Syndrome Knock-in Mouse Model

by Juan J. Salazar, Andrea Satriano, José A. Matamoros, José A. Fernández-Albarral, Elena Salobrar-García, Inés López-Cuenca, Rosa de Hoz, Lidia Sánchez-Puebla, José M. Ramírez, Cristina Alonso, Valentina Satta, Inés Hernández-Fisac, Onintza Sagredo and Ana I. Ramírez

Int. J. Mol. Sci. 2023, 24(3), 2727; https://doi.org/10.3390/ijms24032727 - 01 Feb 2023

Viewed by 3003

Abstract

Dravet syndrome (DS) is an epileptic encephalopathy caused by mutations in the Scn1a gene encoding the α1 subunit of the Nav1.1 sodium channel, which is associated with recurrent and generalized seizures, even leading to death. In experimental models of DS, histological alterations have been found in the brain; however, the retina is a projection of the brain and there are no studies that analyze the possible histological changes that may occur in the disease. This study analyzes the retinal histological changes in glial cells (microglia and astrocytes), retinal ganglion cells (RGCs) and GABAergic amacrine cells in an experimental model of DS (Syn-Cre/Scn1a^WT/A1783V) compared to a control group at postnatal day (PND) 25. Retinal whole-mounts were labeled with anti-GFAP, anti-Iba-1, anti-Brn3a and anti-GAD65/67. Signs of microglial and astroglial activation, and the number of Brn3a+ and GAD65+67+ cells were quantified. We found retinal activation of astroglial and microglial cells but not death of RGCs and GABAergic amacrine cells. These changes are similar to those found at the level of the hippocampus in the same experimental model in PND25, indicating a relationship between brain and retinal changes in DS. This suggests that the retina could serve as a possible biomarker in DS. Full article

(This article belongs to the Special Issue Advanced Research in Retina)

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13 pages, 62543 KiB

Open AccessCommunication

Microglia in Cultured Porcine Retina: Qualitative Immunohistochemical Analyses of Reactive Microglia in the Outer Retina

by Kjell Johansson and Camilla Mohlin

Int. J. Mol. Sci. 2023, 24(1), 871; https://doi.org/10.3390/ijms24010871 - 03 Jan 2023

Viewed by 1757

Abstract

A late stage of several retinal disorders is retinal detachment, a complication that results in rapid photoreceptor degeneration and synaptic damages. Experimental retinal detachment in vivo is an invasive and complicated method performed on anesthetized animals. As retinal detachment may result in visual impairment and blindness, research is of fundamental importance for understanding degenerative processes. Both morphological and ethical issues make the porcine retina a favorable organotypic model for studies of the degenerative processes that follow retinal detachment. In the cultured retina, photoreceptor degeneration and synaptic injuries develop rapidly and correlate with resident microglial cells’ transition into a reactive phenotype. In this immunohistochemical study, we have begun to analyze the transition of subsets of reactive microglia which are known to localize close to the outer plexiform layer (OPL) in degenerating in vivo and in vitro retina. Biomarkers for reactive microglia included P2Ry12, CD63 and CD68 and the general microglial markers were CD11b, Iba1 and isolectin B₄ (IB₄). The reactive microglia markers labeled microglia subpopulations, suggesting that protective or harmful reactive microglia may be present simultaneously in the injured retina. Our findings support the usage of porcine retina cultures for studies of photoreceptor injuries related to retinal detachment. Full article

(This article belongs to the Special Issue Advanced Research in Retina)

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15 pages, 2402 KiB

Open AccessArticle

Examination of Inner Retinal Layers in Unilateral Wet Age-Related Macular Degeneration Treated with Anti-VEGF, Compared to Fellow Untreated Eyes

by Małgorzata Wichrowska, Sławomir Liberski, Anna Rzeszotarska, Przemysław Wichrowski and Jarosław Kocięcki

Int. J. Mol. Sci. 2023, 24(1), 402; https://doi.org/10.3390/ijms24010402 - 26 Dec 2022

Cited by 1 | Viewed by 1361

Abstract

The main aim of this study was to characterize the retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness in the macular area eyes affected by wet age-related macular degeneration (wAMD) treated with anti-VEGF and compare the results with the control of fellow untreated eyes affected by early stages of dry age-related macular degeneration (dAMD). Additionally, we aimed to estimate if the number of injections received and other factors, including age, best-corrected visual acuity (BCVA), or sex, may affect the differences in the obtained measurements of retinal nerve fiber layer thickness. We prospectively included 106 eyes of 53 patients with unilateral wet age-related macular degeneration. The fellow eyes with non-advanced dry age-related macular degeneration served as a control group in a cross-sectional study. RNFL and GCL in the macular region were evaluated using optical coherence tomography, with outcomes expressed as differences in the thickness of both examined layers between the study and control groups. We found thinner GCL in wAMD vs. dAMD (p < 0.001). In turn, the RNFL layer did not show any statistically significant differences between the two groups (p = 0.409). Similarly, we found a statistically significant correlation between the number of injections and the layer thickness (p = 0.106). Among all assessed parameters, age over 73 was the only factor significantly affecting the thickness of the retinal nerve fiber layer in both groups (p = 0.042). The morphology of the inner layers of the retina in dry and wet AMD seems to differ, possibly due to differences in the etiopathogenesis of these two forms of the disease. In our study, the retinal ganglion cell layer was thinner in the treated vs. fellow eye (with dry AMD), while the nerve fiber layer was not significantly different between the groups. The number of anti-VEGF injections had no effect on the thickness of the macular nerve fiber layer. Full article

(This article belongs to the Special Issue Advanced Research in Retina)

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16 pages, 22954 KiB

Open AccessArticle

Purinergic Receptors P2X7 and P2X4 as Markers of Disease Progression in the rd10 Mouse Model of Inherited Retinal Dystrophy

by Natalia Martínez-Gil, Oksana Kutsyr, Agustina Noailles, Laura Fernández-Sánchez, Lorena Vidal, Xavier Sánchez-Sáez, Carla Sánchez-Castillo, Pedro Lax, Nicolás Cuenca, Antonio G. García and Victoria Maneu

Int. J. Mol. Sci. 2022, 23(23), 14758; https://doi.org/10.3390/ijms232314758 - 25 Nov 2022

Cited by 1 | Viewed by 1579

Abstract

The purinergic receptor P2X7 (P2X7R) is implicated in all neurodegenerative diseases of the central nervous system. It is also involved in the retinal degeneration associated with glaucoma, age-related macular degeneration, and diabetic retinopathy, and its overexpression in the retina is evident in these disorders. Retinitis pigmentosa is a progressive degenerative disease that ultimately leads to blindness. Here, we investigated the expression of P2X7R during disease progression in the rd10 mouse model of RP. As the purinergic receptor P2X4 is widely co-expressed with P2X7R, we also studied its expression in the retina of rd10 mice. The expression of P2X7R and P2X4R was examined by immunohistochemistry, flow cytometry, and western blotting. In addition, we analyzed retinal functionality by electroretinographic recordings of visual responses and optomotor tests and retinal morphology. We found that the expression of P2X7R and P2X4R increased in rd10 mice concomitant with disease progression, but with different cellular localization. Our findings suggest that P2X7R and P2X4R might play an important role in RP progression, which should be further analyzed for the pharmacological treatment of inherited retinal dystrophies. Full article

(This article belongs to the Special Issue Advanced Research in Retina)

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21 pages, 3979 KiB

Open AccessArticle

An Exploratory Study Provides Insights into MMP9 and Aβ Levels in the Vitreous and Blood across Different Ages and in a Subset of AMD Patients

by Savannah A. Lynn, Flavie Soubigou, Jennifer M. Dewing, Amanda Smith, Joanna Ballingall, Thea Sass, Isabela Nica, Catrin Watkins, Bhaskar Gupta, Hussein Almuhtaseb, Stephen C. Lash, Ho Ming Yuen, Angela Cree, Tracey A. Newman, Andrew J. Lotery and J. Arjuna Ratnayaka

Int. J. Mol. Sci. 2022, 23(23), 14603; https://doi.org/10.3390/ijms232314603 - 23 Nov 2022

Viewed by 1713

Abstract

Matrix metalloproteinase-9 (MMP9) and total amyloid-beta (Aβ) are prospective biomarkers of ocular ageing and retinopathy. These were quantified by ELISA in the vitreous and blood from controls (n = 55) and in a subset of age-related macular degeneration (AMD) patients (n = 12) for insights and possible additional links between the ocular and systemic compartments. Vitreous MMP9 levels in control and AMD groups were 932.5 ± 240.9 pg/mL and 813.7 ± 157.6 pg/mL, whilst serum levels were 2228 ± 193 pg/mL and 2386.8 ± 449.4 pg/mL, respectively. Vitreous Aβ in control and AMD groups were 1173.5 ± 117.1 pg/mL and 1275.6 ± 332.9 pg/mL, whilst plasma Aβ were 574.3 ± 104.8 pg/mL and 542.2 ± 139.9 pg/mL, respectively. MMP9 and Aβ showed variable levels across the lifecourse, indicating no correlation to each other or with age nor AMD status, though the smaller AMD cohort was a limiting factor. Aβ and MMP9 levels in the vitreous and blood were unrelated to mean arterial pressure. Smoking, another modifiable risk, showed no association with vitreous Aβ. However, smoking may be linked with vitreous (p = 0.004) and serum (p = 0.005) MMP9 levels in control and AMD groups, though this did not reach our elevated (p = 0.001) significance. A bioinformatics analysis revealed promising MMP9 and APP/Aβ partners for further scrutiny, many of which are already linked with retinopathy. Full article

(This article belongs to the Special Issue Advanced Research in Retina)

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9 pages, 988 KiB

Open AccessCommunication

Retinal Oxygen Extraction in Patients with Primary Open-Angle Glaucoma

by Gerhard Garhöfer, Ahmed M. Bata, Alina Popa-Cherecheanu, Anton Hommer, Clemens Vass, Hemma Resch, Doreen Schmidl, René M. Werkmeister and Leopold Schmetterer

Int. J. Mol. Sci. 2022, 23(17), 10152; https://doi.org/10.3390/ijms231710152 - 05 Sep 2022

Cited by 6 | Viewed by 1301

Abstract

Objective: To compare total retinal oxygen extraction between patients with primary open-angle glaucoma (POAG) and healthy control subjects. Design: A prospective, single-center, cross-sectional, case–control study performed at the Medical University of Vienna. Subjects: Forty patients with POAG and 40 age- and sex-matched control subjects. Methods: Total retinal blood flow was measured using Doppler optical coherence tomography (OCT). Retinal arterial and venous oxygen saturation was measured using reflectance spectroscopy. From these parameters, oxygen content in the retinal arterial and venous circulation as well as total retinal oxygen extraction were calculated. Results: Total retinal blood flow was lower in POAG (25.2 ± 6.7 µL/min) as compared to healthy control subjects (35.6 ± 8.3 µL/min, p < 0.001). Retinal arterial oxygen content was not different between the two groups (0.18 ± 0.01 mL(O2)/mL in both groups, p < 0.761), but retinal venous oxygen content was higher in POAG (0.15 ± 0.01 mL(O2)/mL) than in healthy controls (0.14 ± 0.01 mL(O2)/mL p < 0.001). Accordingly, retinal oxygen extraction was reduced in POAG (0.8 ± 0.3 µL(O2)/min as compared to healthy controls: 1.4 ± 0.4 µL(O2)/min, p < 0.001). There was a significant association between total retinal blood flow and total retinal oxygen extraction with measures of structural and functional damage (p < 0.001 each). Conclusions: This study indicates that POAG is associated with a reduction in total retinal oxygen extraction linked to structural and functional damage of the disease. Since the technology is non-invasive, it allows for longitudinal studies investigating to which degree low retinal oxygen extraction is linked to the progression of the disease. Full article

(This article belongs to the Special Issue Advanced Research in Retina)

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15 pages, 3170 KiB

Open AccessArticle

In Vitro Cytotoxicity of D18 and Y6 as Potential Organic Photovoltaic Materials for Retinal Prostheses

by Ana Cetkovic, Alessandro Bellapianta, Mihai Irimia-Vladu, Jakob Hofinger, Cigdem Yumusak, Andrea Corna, Markus Clark Scharber, Günther Zeck, Niyazi Serdar Sariciftci, Matthias Bolz and Ahmad Salti

Int. J. Mol. Sci. 2022, 23(15), 8666; https://doi.org/10.3390/ijms23158666 - 04 Aug 2022

Cited by 1 | Viewed by 2876

Abstract

Millions of people worldwide are diagnosed with retinal dystrophies such as retinitis pigmentosa and age-related macular degeneration. A retinal prosthesis using organic photovoltaic (OPV) semiconductors is a promising therapeutic device to restore vision to patients at the late onset of the disease. However, an appropriate cytotoxicity approach has to be employed on the OPV materials before using them as retinal implants. In this study, we followed ISO standards to assess the cytotoxicity of D18, Y6, PFN-Br and PDIN individually, and as mixtures of D18/Y6, D18/Y6/PFN-Br and D18/Y6/PDIN. These materials were proven for their high performance as organic solar cells. Human RPE cells were put in direct and indirect contact with these materials to analyze their cytotoxicity by the MTT assay, apoptosis by flow cytometry, and measurements of cell morphology and proliferation by immunofluorescence. We also assessed electrophysiological recordings on mouse retinal explants via microelectrode arrays (MEAs) coated with D18/Y6. In contrast to PFN-Br and PDIN, all in vitro experiments show no cytotoxicity of D18 and Y6 alone or as a D18/Y6 mixture. We conclude that D18/Y6 is safe to be subsequently investigated as a retinal prosthesis. Full article

(This article belongs to the Special Issue Advanced Research in Retina)

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Review

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30 pages, 1118 KiB

Open AccessReview

Aflibercept versus Faricimab in the Treatment of Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema: A Review

by Sławomir Liberski, Małgorzata Wichrowska and Jarosław Kocięcki

Int. J. Mol. Sci. 2022, 23(16), 9424; https://doi.org/10.3390/ijms23169424 - 20 Aug 2022

Cited by 27 | Viewed by 10010

Abstract

Diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD) are common retinal vascular diseases responsible for most blindness in the working-age and older population in developed countries. Currently, anti-VEGF agents that block VEGF family ligands, including ranibizumab, bevacizumab (off-label use), brolucizumab, and aflibercept, are the first-line treatment for nAMD and DME. However, due to the complex pathophysiological background of nAMD and DME, non-response, resistance during anti-VEGF therapy, and relapses of the disease are still observed. Moreover, frequent injections are a psychological and economic burden for patients, leading to inadequate adhesion to therapy and a higher risk of complications. Therefore, therapeutic methods are strongly needed to develop and improve, allowing for more satisfactory disease management and lower treatment burden. Currently, the Ang/Tie-2 pathway is a promising therapeutic target for retinal vascular diseases. Faricimab is the first bispecific monoclonal antibody for intravitreal use that can neutralize VEGF and Ang-2. Due to the prolonged activity, faricimab allows extending the interval between successive injections up to three or four months in nAMD and DME patients, which can be a significant benefit for patients and an alternative to implanted drug delivery systems. Full article

(This article belongs to the Special Issue Advanced Research in Retina)

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24 pages, 2573 KiB

Open AccessReview

Sigma-1 Receptor in Retina: Neuroprotective Effects and Potential Mechanisms

by Zifen Xu, Yushuang Lei, Huan Qin, Shiyao Zhang, Ping Li and Kai Yao

Int. J. Mol. Sci. 2022, 23(14), 7572; https://doi.org/10.3390/ijms23147572 - 08 Jul 2022

Cited by 6 | Viewed by 2553

Abstract

Retinal degenerative diseases are the major factors leading to severe visual impairment and even irreversible blindness worldwide. The therapeutic approach for retinal degenerative diseases is one extremely urgent and hot spot in science research. The sigma-1 receptor is a novel, multifunctional ligand-mediated molecular chaperone residing in endoplasmic reticulum (ER) membranes and the ER-associated mitochondrial membrane (ER-MAM); it is widely distributed in numerous organs and tissues of various species, providing protective effects on a variety of degenerative diseases. Over three decades, considerable research has manifested the neuroprotective function of sigma-1 receptor in the retina and has attempted to explore the molecular mechanism of action. In the present review, we will discuss neuroprotective effects of the sigma-1 receptor in retinal degenerative diseases, mainly in aspects of the following: the localization in different types of retinal neurons, the interactions of sigma-1 receptors with other molecules, the correlated signaling pathways, the influence of sigma-1 receptors to cellular functions, and the potential therapeutic effects on retinal degenerative diseases. Full article

(This article belongs to the Special Issue Advanced Research in Retina)

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