Bowman lecture on the role of inflammation in degenerative disease of the eye

Abstract

Inflammation, in the pathogenesis of many diseases previously thought to be strictly genetic, degenerative, metabolic, or endocrinologic in aetiology, has gradually entered the framework of a general mechanism of disease. This is exemplified by conditions such as Parkinson's disease, Alzheimer's disease, atherosclerosis, diabetes, and the more recently described Metabolic Syndrome. Chronic inflammatory processes have a significant, if not primary role, in ophthalmic diseases, particularly in retinal degenerative diseases. However, inflammation itself is not easy to define, and some aspects of inflammation may be beneficial, in a process described as 'para-inflammation' by Medhzitov. In contrast, the damaging effects of inflammation, mediated by pro-inflammatory macrophages through activation of the intracellular protein-signalling complexes, termed inflammasomes, are well recognised and are important therapeutic targets. In this review, the range of inflammatory processes in the eye is evaluated in the context of how these processes impact upon retinal degenerative disease, particularly diabetic retinopathy and age-related macular degeneration.

Figure 1

Kinetics of inflammatory cell infiltration into the retina. The development of EAU in the mouse was evaluated in vivo using SLO by adoptive transfer of labelled T cells into mice who had been immunised with IRPB peptides 161–180 and flat mount preparations of the retinal tissue. Seven days after immunisation, the first change observed was a decline in shear stress and in increase in adhesion molecule expression on the endothelium of the retinal vessels. This was followed by breakdown of the blood retinal barrier and infiltration of T cells into the retinal tissue, which maximally occurred 9 days after immunisation. Courtesy Dr Heping Xu.

Figure 2

(a) Cartoon demonstrating a possible mechanism for neovascularisation arising from an occluded post-capillary venule; (b) intravascular neovascularisation (1) showing a small neovessel filled with red blood cells in an occluded vessel in a case of diabetic retinopathy. Note the intravascular nuclei from migrating endothelial cells in the area of previous occlusion (2). Haematoxylin and eosin stain courtesy of Professor WR Lee.

Figure 3

Pathology of dry AMD showing geographic atrophy. Note junction (arrow) of a patch of geographic atrophic retina (absence of photoreceptors and damaged/loss of RPE cells) with area of retina choroid where RPE and photoreceptors cells are still present. Mallory Trichrome stain. Section courtesy of Professor WR Lee.