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Inflammation, Fibrosis and Neovascularisation: New Perspectives for Old Foes in the Pathogenesis of Neovascular AMD

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (30 January 2024) | Viewed by 2677

Special Issue Editors


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Guest Editor
Department of Anatomy and Neuroscience, University of Melbourne, Parkville 002153M, Australia
Interests: macular degeneration; photoreceptors; retina; immune system; ophthalmology; bionic eye; glia

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Guest Editor
ANU College of Health and Medicine, Australian National University, Canberra, ACT 2601, Australia
Interests: eyes in ageing and disease

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Guest Editor
Karolinska Institutet, St. Erik Eye Hospital, 11282 Stockholm, Sweden
Interests: age-related macular degeneration; inherited retinal degenerations; regenerative medicine; gene therapy

Special Issue Information

Dear Colleagues,

Choroidal neovascularisation manifests in advanced macular degeneration as a pathological growth of blood vessels in the choroid. The new blood vessel growth resulting from the choroid is leaky and, if untreated, leads to severe vision loss. Choroidal neovascularisation is akin to a maladaptive wound-healing response. The remodeled choroidal tissue environment is fibrotic and pro-inflammatory. Treatments that target neovascular-promoting factors (e.g., vascular endothelial growth factor and angiopoietin) have revolutionised our ability to prevent vision loss in neovascular macular degeneration. However, vision loss can continue to occur as treatments are unable to treat the subretinal fibrosis and inflammation that accompanies choroidal neovascularisation. Improving our understanding of the molecular processes that underpin these responses is, therefore, crucial to help ameliorate vision loss in neovascular macular degeneration.

For this Special Issue, we would like to invite papers that investigate and discuss the molecular signaling that drives choroidal neovascularisation pathogenesis and/or diagnosis or treatments. Suggested areas are molecular mechanisms of neovascularisation, fibrosis, and inflammation that regulate choroidal neovascularisation in preclinical or clinical settings. This includes novel treatment approaches that target or incorporate gene and cell therapies for choroidal neovascularization and identification or proposal of potential biomarkers (e.g., imaging, blood, or eye fluid) that are either implicated or associated with choroidal neovascularisation. Clinical research that includes molecular mechanism studies will also be welcomed.

Dr. Alice Brandli
Dr. Matt Rutar
Dr. Helder Andre
Guest Editors

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Keywords

  • macular degeneration
  • age-related macular degeneration
  • angiogenesis
  • choroidal neovascularisation
  • fibrosis
  • wound healing
  • retinal pigment epithelium
  • choroid
  • optical coherance tomography
  • biomarkers
  • inflammation
  • complement
  • endothelial growth factor
  • growth factor

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Published Papers (1 paper)

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Review

16 pages, 1981 KiB  
Review
CRISPR Manipulation of Age-Related Macular Degeneration Haplotypes in the Complement System: Potential Future Therapeutic Applications/Avenues
by Ahmed Salman, Michelle E. McClements and Robert E. MacLaren
Int. J. Mol. Sci. 2024, 25(3), 1697; https://doi.org/10.3390/ijms25031697 - 30 Jan 2024
Cited by 3 | Viewed by 2217
Abstract
Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among the elderly in the developed world. Whilst AMD is a multifactorial disease, the involvement of the complement system in its pathology is well documented, with single-nucleotide polymorphisms (SNPs) in different [...] Read more.
Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among the elderly in the developed world. Whilst AMD is a multifactorial disease, the involvement of the complement system in its pathology is well documented, with single-nucleotide polymorphisms (SNPs) in different complement genes representing an increased risk factor. With several complement inhibitors explored in clinical trials showing limited success, patients with AMD are still without a reliable treatment option. This indicates that there is still a gap of knowledge in the functional implications and manipulation of the complement system in AMD, hindering the progress towards translational treatments. Since the discovery of the CRISPR/Cas system and its development into a powerful genome engineering tool, the field of molecular biology has been revolutionised. Genetic variants in the complement system have long been associated with an increased risk of AMD, and a variety of haplotypes have been identified to be predisposing/protective, with variation in complement genes believed to be the trigger for dysregulation of the cascade leading to inflammation. AMD-haplotypes (SNPs) alter specific aspects of the activation and regulation of the complement cascade, providing valuable insights into the pathogenic mechanisms of AMD with important diagnostic and therapeutic implications. The effect of targeting these AMD-related SNPs on the regulation of the complement cascade has been poorly explored, and the CRISPR/Cas system provides an ideal tool with which to explore this avenue. Current research concentrates on the association events of specific AMD-related SNPs in complement genes without looking into the effect of targeting these SNPs and therefore influencing the complement system in AMD pathogenesis. This review will explore the current understanding of manipulating the complement system in AMD pathogenesis utilising the genomic manipulation powers of the CRISPR/Cas systems. A number of AMD-related SNPs in different complement factor genes will be explored, with a particular emphasis on factor H (CFH), factor B (CFB), and complement C3 (C3). Full article
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