Complement System and the Eye

Jha, Purushottam; Bora, Puran S.; Sohn, Jong Hee; Kaplan, Henry J.; Bora, Nalini S.

doi:10.1007/0-387-34134-x_4

Cited by 8 publications

(7 citation statements)

References 34 publications

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“…Vascular inflammation and activation of the complement system are of significance in many tissues and are especially critical for the brain and retina, where complement activation can disrupt the normal blood-brain and blood-retina barriers (1,2). Because proinflammatory changes contributing to blood-retina barrier breakdown represent an important initiating factor in the pathogenesis of diabetic retinopathy (DR) (3), and because activation of the complement system and impairment of complement regulatory proteins were observed in the eyes of patients with DR and in animal models of DR (1,4,5), this study addressed the role of complement activation in vascular damage in animal and ex vivo models of DR.…”

Section: Introductionmentioning

confidence: 99%

Plasma Exosomes Contribute to Microvascular Damage in Diabetic Retinopathy by Activating the Classical Complement Pathway

et al. 2018

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Diabetic retinopathy (DR) is a microvascular complication of diabetes and is the leading cause of vision loss in working-age adults. Recent studies have implicated the complement system as a player in the development of vascular damage and progression of DR. However, the role and activation of the complement system in DR are not well understood. Exosomes, small vesicles that are secreted into the extracellular environment, have a cargo of complement proteins in plasma, suggesting that they can participate in causing the vascular damage associated with DR. We demonstrate that IgG-laden exosomes in plasma activate the classical complement pathway and that the quantity of these exosomes is increased in diabetes. Moreover, we show that a lack of IgG in exosomes in diabetic mice results in a reduction in retinal vascular damage. The results of this study demonstrate that complement activation by IgG-laden plasma exosomes could contribute to the development of DR.

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Section: Introductionmentioning

confidence: 99%

Plasma Exosomes Contribute to Microvascular Damage in Diabetic Retinopathy by Activating the Classical Complement Pathway

et al. 2018

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“…The aqueous humour contains complement factors and their inhibitors. 24 It may also contain proteins, such as thrombospondin, that contribute to the local activation of TGF- β . 25 Altogether, the healthy ocular microenvironment places a high threshold to be overcome for the induction of inflammation and immunity within its tissue microenvironment.…”

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confidence: 99%

Ocular immune privilege

Taylor

2009

Eye

187

141

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It has been over 60 years since the phrase immune privilege was used by Sir Peter Medawar to describe the lack of an immune response against allografts placed into the ocular microenvironment. Since then, we have come to understand that the mechanisms of ocular immune privilege include unique anatomical features of a blood barrier and a lack of direct lymphatic drainage. Also, we know that the ocular microenvironment is rich with immunosuppressive molecules that influence the activity of immune cells. Moreover, the placement of foreign antigen into the ocular microenvironment can induce a systemic form of tolerance to the foreign antigen called anterior chamber-associated immune deviation (ACAID). Many soluble immunomodulators are found in aqueous humour, and are a mixture of growth factors, cytokines, neuropeptides, and soluble receptors. This is a continuously growing list. The mechanisms of ocular immune privilege induce apoptosis, promote the production of anti-inflammatory cytokines, and mediate the activation of antigen-specific regulatory immunity. These mechanisms of immune privilege also attempt to impose themselves upon immunity within the uveitic eye. The adaptation of several anatomical and biochemical mechanisms to establish an immune privileged microenvironment within the eye makes the eye immunologically unique. It is a tissue site where we may learn how immunity is regulated in inflammation and at rest. Success in translating the lessons of ocular immune privilege to other tissues has the potential to drastically change the therapy and clinical outcomes of autoimmune diseases and allograft survival.

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“…It is well known that MAC formation is a measure of complement activation (Bora et al, 2008; Jha et al, 2006, 2007) and GFAP expression increases in eyes with increased IOP (Woldemussie et al, 2004). The immunostaining of paraffin embedded sections demonstrated the presence of basal levels of GFAP (red fluorescence in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In the current study we used CVF to deplete the complement system. To confirm that repeated CVF injections deplete the complement system of the host, complement activity was checked on every seventh day post-laser using hemolytic assay as described previously by us (Jha et al, 2006). Complement activity (as measured by hemolytic assay) was barely detectable in rats that received repeated injections of CVF (data not shown).…”

Section: Discussionmentioning

confidence: 99%

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Complement mediated apoptosis leads to the loss of retinal ganglion cells in animal model of glaucoma

Jha

Banda

Tytarenko

et al. 2011

Molecular Immunology

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This study investigated the role of complement in the protection of retinal ganglion cells (RGCs) in chronic ocular hypertension model of glaucoma. Intraocular pressure (IOP) was elevated in the right eye of Lewis rats by laser photocoagulation (two treatments, 7 days apart) of episcleral and limbal veins. Left eye did not receive laser treatment and served as control. Animals were injected with cobra venom factor every fifth day starting day 7 after first laser, to deplete the complement system. Animals were sacrificed at six week post-laser. Levels of C3 split products and membrane attack complex (MAC) were elevated in the retina of eyes with increased IOP and complement depletion reduced the loss of Brn3a+ RGCs accompanied by decreased expression of GFAP and reduced MAC deposition. In complement depleted rats with increased IOP, reduced TUNEL+ cells in ganglion cell layer, and decreased levels of active caspase-8 and active caspase-9 was observed compared to PBS treated complement sufficient rats with increased IOP. Interestingly, complement depletion also resulted in reduction of calcium influx and levels of BAD in the retinal cells of the eyes with increased IOP. Together, our results provide evidence that complement mediated apoptosis plays a pivotal role in the loss of RGCs in chronic ocular hypertension model of glaucoma.

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Complement System and the Eye

Cited by 8 publications

References 34 publications

Plasma Exosomes Contribute to Microvascular Damage in Diabetic Retinopathy by Activating the Classical Complement Pathway

Plasma Exosomes Contribute to Microvascular Damage in Diabetic Retinopathy by Activating the Classical Complement Pathway

Ocular immune privilege

Complement mediated apoptosis leads to the loss of retinal ganglion cells in animal model of glaucoma

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