THE EYES HAVE IT ALL!

Abstract

Lack of systematic studies on the role of inflammation in age-associated chronic diseases, including multistep carcinogenesis has been extremely costly for taxpayers and patients. Recently, unresolved/chronic inflammation was defined as loss of balance between two tightly regulated and biologically opposing arms of acute inflammation (Yin–Yang or immune surveillance). Analyses of a series of data on ‘accidental’ discoveries that were established in 1980s on models of acute and chronic ocular inflammatory diseases in conjunctival-associated lymphoid tissues (CALTs) revealed at least three stages of clinical and immunological findings including earliest immune disruptor-induced changes in immune response profiles. Inflammation-induced interactions between resident (host) and recruited immune cells included: (a), acute phase, early immune disruptor-induced strong clinical reactions and tearing, activation and effector response from mast cells (MCs) and B/plasma cells, biosynthesis of IgE Abs, release of histamine and biosynthesis of prostaglandin PGF1α; (b), intermediate phase, down-regulation phenomenon, minimal clinical response, exhausted/degranulated MCs, heavy eosinophils (Eos) infiltrations into epithelium and mucus secreting goblet cells (GCs), tissue hypertrophy and neovascularization; and (c), chronic phase; induction of lymphoid hyperplasia, activated macrophages (MΦs), increased (irregular size) B and plasma cells, loss of integrity of lymphoid tissue capsular membrane, presence of histiocytes (activities of dendritic cell phenotype), follicular and germinal center formation, increased ratios of local IgG1/IgG2, epithelial thickening (growth) and/or thinning (necrosis) often noted in the same tissue sections and angiogenesis. Results of these systematic studies are suggestive of first series of evidence for direct association between inflammation and identifiable multistep immune dysfunction in the direction of tumorigenesis. Systematic studies to monitor interactions between resident and recruited cells in site-specific tissues should provide key information not only for identification of immune disruptor-induced early events in the loss of immune surveillance, but they would help making informed decisions for balancing the inherent tumoricidal (Yin) and tumorigenic (Yang) properties of immune system for effective preventive and therapeutic approaches and accurate risk assessment toward improvement of public health.