Immunology and Pathology in Ocular Drug Development

Clear vision is dependent on features that protect the anatomical integrity of the eye (cornea and sclera) and those that contribute to internal ocular homeostasis by conferring hemangiogenic (avascular tissues and antiangiogenic factors), lymphangiogenic (lack of draining lymphatics), and immunologic (tight junctions that form blood–ocular barriers, immunosuppressive cells, and modulators) privileges. The later examples are necessary components that enable the eye to maintain an immunosuppressive environment that responds to foreign invaders in a deviated manner, minimizing destructive inflammation that would impair vision. These conditions allowed for the observations made by Medawar, in 1948, of delayed rejection of allogenic tissue grafts in the anterior chamber of mouse eye and permit the sequestration of foreign invaders (eg, Toxoplasma gondii) within the retina of healthy individuals. Yet successful development of intraocular drugs (biologics and delivery devices) has been stymied by adverse ocular pathology, much of which is driven by immune pathways. The eye can be intolerant of foreign protein irrespective of delivery route, and endogenous ocular cells have remarkable plasticity when recruited to preserve visual function. This article provides a review of current understanding of ocular immunology and the potential role of immune mechanisms in pathology observed with intraocular drug delivery.

IFNγ modulates human immunoglobulin receptor expression in lipoaspirate-derived mesenchymal stem cells

Background: Mesenchymal stem cell (MSC) has been reported to have immunomodulator capacity against autoimmune diseases and to prevent allogenic tissue rejection. Many studies revealed that MSC’s inhibit T cell proliferation and induce immunosuppressive condition through the production of prostaglandins, and interleukin-10. In addition, MSC was reported to reduce circulating autoantibody in autoimmune patients following MSC transfusion. So far, there has been no report stating the presence of Fc receptors (receptors for immunoglobulin) on MSCs. The aim of this study was to reveal the expression of FcγRs in lipoaspirate-derived MSCs by measuring transcription of FcγR mRNA and whether the expression can be modulated.Methods: Lipoaspirate-derived MSCs were cultured in suitable medium and confirmed to be MSCs according to the criteria published by International Society for Cellular Therapy. Total mRNA of MSCs was isolated, and detection of human FcγRI, FcγRIIA and FcγRIIB mRNA was performed. Further, modulation of the expression was tested using heat aggregated gamma globulin (HAGG) and interferon (IFN)γ.Results: FcγRs mRNA was detected in the first passage of MSCs. However, the expression was no longer present after more than 4 passages. Further, increased level of FcγRI and FcγRIIA mRNA expression was detected with the addition of IFNγ in the culture. This preliminary finding opens a new insight for the understanding of interaction between MSCs and immunoglobulin G through FcγRs.Conclusion: Lipoaspirate-derived MSCs express FcγRs, and the expression is modulated by IFNγ.