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Life
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Retinal Diseases: From Molecular Mechanisms to Therapeutics
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Retinal Diseases: From Molecular Mechanisms to Therapeutics

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Physiology and Pathology".

Deadline for manuscript submissions: 30 January 2025 | Viewed by 6587

Special Issue Editor

Dr. Soo-Young Kim

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Guest Editor
Independent Researcher and Consultant for Biopharma Research and Development, Carlsbad, CA, USA
Interests: brain and retina inflammatory diseases; ocular immunology; macrophage; gene and cell therapy; exosome; viral vector; gene delivery; antibody; biologics; bioprocess

Special Issue Information

Dear Colleague,

The aim of this Special Issue is to provide an update of general and genetic retinal diseases and associated molecular pathways and the current stage which the therapeutics approaches are at. General retina diseases include age-related macular degeneration, glaucoma, diabetic retinopathy, uveitis, etc. Additionally, genetic retina diseases are not limited, including Leber congenital amaurosis, retinitis pigmentosa, retinoschisis, Stargardt diseases, etc. The most updated therapeutic development approaches and related molecular pathways and pathological aspects of retina diseases will be described and discussed in this Special Issue. The related molecular pathway will be described, and drug development approaches have no limitations, including small molecules, antibodies, peptides, cell and gene therapy, exosomes microbiomes, etc. The Special Issue will provide insights into the validated and developing approaches toward the development of therapeutics in retinal diseases.

Dr. Soo-Young Kim
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. Life is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • retinal disease
  • inflammatory disease
  • genetic diseases
  • ocular drug development

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Published Papers (5 papers)

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Research

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22 pages, 10840 KiB  
Article
Murine Retina Outer Plexiform Layer Development and Transcriptome Analysis of Pre-Synapses in Photoreceptors
by Soo-Young Kim, Christine Haewon Park, Bo-Hyun Moon and Gail K. Seabold
Life 2024, 14(9), 1103; https://doi.org/10.3390/life14091103 - 2 Sep 2024
Viewed by 833
Abstract
Photoreceptors in the mammalian retina convert light signals into electrical and molecular signals through phototransduction and transfer the visual inputs to second-order neurons via specialized ribbon synapses. Two kinds of photoreceptors, rods and cones, possess distinct morphology and function. Currently, we have limited [...] Read more.
Photoreceptors in the mammalian retina convert light signals into electrical and molecular signals through phototransduction and transfer the visual inputs to second-order neurons via specialized ribbon synapses. Two kinds of photoreceptors, rods and cones, possess distinct morphology and function. Currently, we have limited knowledge about rod versus (vs.) cone synapse development and the associated genes. The transcription factor neural retina leucine zipper (NRL) determines the rod vs. cone photoreceptor cell fate and is critical for rod differentiation. Nrl knockout mice fail to form rods, generating all cone or S-cone-like (SCL) photoreceptors in the retina, whereas ectopic expression of Nrl using a cone-rod homeobox (Crx) promoter (CrxpNrl) forms all rods. Here, we examined rod and cone pre-synapse development, including axonal elongation, terminal shaping, and synaptic lamination in the outer plexiform layer (OPL) in the presence or absence of Nrl. We show that NRL loss and knockdown result in delayed OPL maturation and plasticity with aberrant dendrites of bipolar neurons. The integrated analyses of the transcriptome in developing rods and SCLs with NRL CUT&RUN and synaptic gene ontology analyses identified G protein subunit beta (Gnb) 1 and p21 (RAC1) activated kinase 5 (Pak5 or Pak7) transcripts were upregulated in developing rods and down-regulated in developing SCLs. Notably, Gnb1 and Gnb5 are rod dominant, and Gnb3 is enriched in cones. NRL binds to the genes of Gnb1, Gnb3, and Gnb5. NRL also regulates pre-synapse ribbon genes, and their expression is altered in rods and SCLs. Our study of histological and gene analyses provides new insights into the morphogenesis of photoreceptor pre-synapse development and regulation of associated genes in the developing retina. Full article
(This article belongs to the Special Issue Retinal Diseases: From Molecular Mechanisms to Therapeutics)
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11 pages, 1289 KiB  
Article
Intravitreal Antiangiogenic Treatment for Diabetic Retinopathy: A Mexican Real-Life Scenario Experience
by Sonia López-Letayf, Oscar Vivanco-Rojas, Valentina Londoño-Angarita, Fátima Sofía Magaña-Guerrero, Beatriz Buentello-Volante and Yonathan Garfias
Life 2024, 14(8), 976; https://doi.org/10.3390/life14080976 - 2 Aug 2024
Viewed by 705
Abstract
The objective of this study was to analyze the effectiveness of two intravitreal antiangiogenic drugs, ranibizumab and aflibercept, in a Mexican population over a period of 5 years, evaluating the improvement in visual acuity (VA) and central retinal thickness (CRT) in a real-world [...] Read more.
The objective of this study was to analyze the effectiveness of two intravitreal antiangiogenic drugs, ranibizumab and aflibercept, in a Mexican population over a period of 5 years, evaluating the improvement in visual acuity (VA) and central retinal thickness (CRT) in a real-world scenario. This is a retrospective study with subjects diagnosed with diabetic retinopathy (DR), proliferative diabetic retinopathy (PDR), and diabetic macular edema (DME) receiving intravitreal injections of ranibizumab and/or aflibercept. In this study, we analyzed 588 eyes of 294 patients who received intravitreal antiangiogenic injections. The results showed an improvement regardless of antiangiogenic treatment or diagnosis in both VA and CRT. We found that both aflibercept and ranibizumab improved VA, while subjects with DME responded less to antiangiogenic treatment (p < 0.05), and that this difference did not correspond to the CRT measured by OCT. These results support evidence that intravitreal antiangiogenic medications are effective for ophthalmic complications of diabetes in our population; however, damage to visual structures is not reversed in most patients. And that the perception by the patient (VA) and that of the ophthalmologist (CRT) do not completely correlate in our study. Full article
(This article belongs to the Special Issue Retinal Diseases: From Molecular Mechanisms to Therapeutics)
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12 pages, 3000 KiB  
Article
Use of VESsel GENeration with Optical Coherence Tomography Angiography and Fluorescein Angiography for Detection and Quantification of Vascular Changes in Mild and Moderate Diabetic Retinopathy
by Mariana DuPont, Edmund Arthur, Yazen Shihab, Madelyn Kenny, Swetha Ravichandran, Patricia Parsons-Wingerter, Ruchi Vyas, Matthew C. Murray, Marina Predovic, Shiyin Lim, Nicole Jacobs, Sneha Ramesh, Amanda Vu, Srinivaas Sekaran, Kakarla V. Chalam, Ramana S. Moorthy, Jason Crosson, John Mason and Maria B. Grant
Life 2024, 14(7), 893; https://doi.org/10.3390/life14070893 - 18 Jul 2024
Cited by 1 | Viewed by 913
Abstract
(1) Background: Previously, VESsel GENeration (VESGEN) software was used to map and quantify vascular changes observed on fluorescein angiography (FA) in subjects (n = 15 eyes) with retinal pathology ranging from mild non-proliferative diabetic retinopathy (NPDR) to proliferative diabetic retinopathy (PDR). In the [...] Read more.
(1) Background: Previously, VESsel GENeration (VESGEN) software was used to map and quantify vascular changes observed on fluorescein angiography (FA) in subjects (n = 15 eyes) with retinal pathology ranging from mild non-proliferative diabetic retinopathy (NPDR) to proliferative diabetic retinopathy (PDR). In the current study, we used VESGEN for the assessment of individuals with early-stage NPDR imaged by FA (Cohort 1) and by optical coherence tomography angiography (OCTA; Cohort 2). (2) Methods: Cohort 1 included type 2 diabetics (T2D), represented 21 eyes (ranging from no DR to moderate DR), and also included nondiabetic controls (NDC; n = 15 eyes). Cohort 2 consisted of 23 eyes from T2D subjects (including no DR subjects and moderate DR subjects) and NDC (n = 18 eyes). (3) Results: In the FA-VESGEN study, total tortuosity (Tv) of microvessels (G ≥ 6) increased in T2D with mild DR compared to the controls. In contrast, the VESGEN analysis of OCTA images showed that vessel length (characterized as density) was lower in T2D subjects before the diagnosis of DR and following the diagnosis of DR when compared to the controls. Additionally, T2D showed a significant decrease in vessel area (density). (4) Conclusions: FA elucidated the vessel morphology of small-generation microvessels to a greater degree than OCTA; however, OCTA identified changes in vessel density better than FA. VESGEN analysis can be used with both standard FA and OCTA to facilitate our understanding of early events in DR, including before the clinical diagnosis of DR. Full article
(This article belongs to the Special Issue Retinal Diseases: From Molecular Mechanisms to Therapeutics)
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14 pages, 2962 KiB  
Article
Investigation of PACAP38 and PAC1 Receptor Expression in Human Retinoblastoma and the Effect of PACAP38 Administration on Human Y-79 Retinoblastoma Cells
by Dénes Tóth, Eszter Fábián, Edina Szabó, Evelin Patkó, Viktória Vicena, Alexandra Váczy, Tamás Atlasz, Tamás Tornóczky and Dóra Reglődi
Life 2024, 14(2), 185; https://doi.org/10.3390/life14020185 - 26 Jan 2024
Viewed by 1311
Abstract
Retinoblastoma represents the most prevalent malignant neoplasm affecting the eyes in childhood. The clear-cut origin of retinoblastoma has not yet been determined; however, based on experiments, it has been suggested that RB1 loss in cone photoreceptors causes retinoblastoma. Pituitary adenylate-cyclase activating polypeptide (PACAP) [...] Read more.
Retinoblastoma represents the most prevalent malignant neoplasm affecting the eyes in childhood. The clear-cut origin of retinoblastoma has not yet been determined; however, based on experiments, it has been suggested that RB1 loss in cone photoreceptors causes retinoblastoma. Pituitary adenylate-cyclase activating polypeptide (PACAP) is a pleiotropic neuropeptide which has been shown to be affected in certain tumorous transformations, such as breast, lung, kidney, pancreatic, colon, and endocrine cancers. This study aimed to investigate potential changes in both PACAP38 and PAC1 receptor (PAC1R) expression in human retinoblastoma and the effect of PACAP38 administration on the survival of a human retinoblastoma cell line (Y-79). We analyzed human enucleation specimens removed because of retinoblastoma for PACAP38 and PAC1R immunostaining and the effect of PACAP38 on the survival of the Y-79 cell line. We described for the first time that human retinoblastoma cells from patients showed only perinuclear, dot-like immunopositivity for both PACAP38 and PAC1R, irrespective of laterality, genetic background, or histopathological features. Nanomolar (100 nM and 500 nM) PACAP38 concentrations had no effect on the viability of Y-79 cells, while micromolar (2 µM and 6 µM) PACAP38 significantly decreased tumor cell viability. These findings, along with general observations from animal studies showing that PACAP38 has strong anti-apoptotic, anti-inflammatory, and antioxidant effects on ocular tissues, together suggest that PACAP38 and its analogs are promising candidates in retinoblastoma therapy. Full article
(This article belongs to the Special Issue Retinal Diseases: From Molecular Mechanisms to Therapeutics)
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Review

Jump to: Research

19 pages, 326 KiB  
Review
Exploring Stem-Cell-Based Therapies for Retinal Regeneration
by Madalina Radu, Daniel Constantin Brănișteanu, Ruxandra Angela Pirvulescu, Otilia Maria Dumitrescu, Mihai Alexandru Ionescu and Mihail Zemba
Life 2024, 14(6), 668; https://doi.org/10.3390/life14060668 - 23 May 2024
Cited by 2 | Viewed by 2122
Abstract
The escalating prevalence of retinal diseases—notably, age-related macular degeneration and hereditary retinal disorders—poses an intimidating challenge to ophthalmic medicine, often culminating in irreversible vision loss. Current treatments are limited and often fail to address the underlying loss of retinal cells. This paper explores [...] Read more.
The escalating prevalence of retinal diseases—notably, age-related macular degeneration and hereditary retinal disorders—poses an intimidating challenge to ophthalmic medicine, often culminating in irreversible vision loss. Current treatments are limited and often fail to address the underlying loss of retinal cells. This paper explores the potential of stem-cell-based therapies as a promising avenue for retinal regeneration. We review the latest advancements in stem cell technology, focusing on embryonic stem cells (ESCs), pluripotent stem cells (PSCs), and mesenchymal stem cells (MSCs), and their ability to differentiate into retinal cell types. We discuss the challenges in stem cell transplantation, such as immune rejection, integration into the host retina, and functional recovery. Previous and ongoing clinical trials are examined to highlight the therapeutic efficacy and safety of these novel treatments. Additionally, we address the ethical considerations and regulatory frameworks governing stem cell research. Our analysis suggests that while stem-cell-based therapies offer a groundbreaking approach to treating retinal diseases, further research is needed to ensure long-term safety and to optimize therapeutic outcomes. This review summarizes the clinical evidence of stem cell therapy and current limitations in utilizing stem cells for retinal degeneration, such as age-related macular degeneration, retinitis pigmentosa, and Stargardt’s disease. Full article
(This article belongs to the Special Issue Retinal Diseases: From Molecular Mechanisms to Therapeutics)
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