The extracellular microenvironment in immune dysregulation and inflammation in retinal disorders

Fabiola Biasella; Karolina Plössl; Paul N Baird; Bernhard H F Weber

doi:10.3389/fimmu.2023.1147037

The extracellular microenvironment in immune dysregulation and inflammation in retinal disorders

Front Immunol. 2023 Mar 1:14:1147037. doi: 10.3389/fimmu.2023.1147037. eCollection 2023.

Authors

Fabiola Biasella¹, Karolina Plössl¹, Paul N Baird^{1

2}, Bernhard H F Weber^{1

3}

Affiliations

¹ Institute of Human Genetics, University of Regensburg, Regensburg, Germany.
² Department of Surgery, Ophthalmology, University of Melbourne, Melbourne, VIC, Australia.
³ Institute of Clinical Human Genetics, University Hospital Regensburg, Regensburg, Germany.

Abstract

Inherited retinal dystrophies (IRDs) as well as genetically complex retinal phenotypes represent a heterogenous group of ocular diseases, both on account of their phenotypic and genotypic characteristics. Therefore, overlaps in clinical features often complicate or even impede their correct clinical diagnosis. Deciphering the molecular basis of retinal diseases has not only aided in their disease classification but also helped in our understanding of how different molecular pathologies may share common pathomechanisms. In particular, these relate to dysregulation of two key processes that contribute to cellular integrity, namely extracellular matrix (ECM) homeostasis and inflammation. Pathological changes in the ECM of Bruch's membrane have been described in both monogenic IRDs, such as Sorsby fundus dystrophy (SFD) and Doyne honeycomb retinal dystrophy (DHRD), as well as in the genetically complex age-related macular degeneration (AMD) or diabetic retinopathy (DR). Additionally, complement system dysfunction and distorted immune regulation may also represent a common connection between some IRDs and complex retinal degenerations. Through highlighting such overlaps in molecular pathology, this review aims to illuminate how inflammatory processes and ECM homeostasis are linked in the healthy retina and how their interplay may be disturbed in aging as well as in disease.

Keywords: Bruch’s membrane; Sorsby fundus dystrophy; TIMP3; age-related macular degeneration; extracellular matrix; inflammation; matricellular proteins; retinal disease.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Humans
Inflammation / pathology
Macular Degeneration* / genetics
Optic Disk Drusen* / pathology
Retina / pathology

Supplementary concepts

Doyne honeycomb retinal dystrophy

Grants and funding

This research was funded by the Australian National Health and Medical Research Council (NHMRC) Senior Research Fellowship grant number 1138585 to PB. The sponsor or funding organizations had no role in the design or conduct of this research.