Is our current clinical classification of AMD up to the job?
Explore the source record for details and available documents.
Environment↗
Biomedical subjects
S W Cousins
Publications and source records attributed to S W Cousins.
Cell-mediated cytotoxicity of murine cytomegalovirus-infected target cells allows for release of residual infectious virus.
Although cell-mediated cytotoxicity effectively kills target virus-infected cells, no careful consideration has been given to the fate of infectious progeny virus contained within target cells following the cytolytic event. To address this issue with respect to murine cytomegalovirus (MCMV) pathogenesis, we developed a rapid semiquantitative assay for infectious MCMV based on expression of beta-galactosidase using a LacZ-expressing recombinant MCMV. Simultaneous use of this assay in combination with a modified cell-mediated cytotoxicity assay revealed that cytotoxicity of MCMV-infected target cells mediated by MCMV-immune splenic cells does not lead to inactivation of intracellular infectious virus.
Animals↗
Perforin knockout mice, but not mice with MAIDS, show protection against experimental cytomegalovirus retinitis after adoptive transfer of immune cells with a functional perforin cytotoxic pathway.
Adoptive transfer studies were performed to test the hypothesis that the perforin cytotoxic pathway is more important than the Fas/FasL cytotoxic pathway in protection against experimental murine cytomegalovirus (MCMV) retinitis. Splenic immune cells from donor MCMV-immunized normal mice or gld mice deficient in Fas/FasL-mediated cytotoxicity significantly reduced the frequency and severity of MCMV retinitis following subretinal MCMV challenge when transferred into recipient PKO mice deficient in perforin-mediated cytotoxicity. In sharp contrast, splenic cells from donor MCMV-immunized PKO mice failed to provide protection against MCMV retinitis when transferred into recipient PKO mice. Protection was not achieved, however, in recipient mice with retrovirus-induced immunodeficiency (MAIDS), even when splenic cells originated from MCMV-immunized normal mice.
Adoptive Transfer↗
Regulated heat shock protein 27 expression in human retinal pigment epithelium.
PURPOSE: To examine the expression and regulation of an injury-related protein, heat shock protein (Hsp) 27, in retinal pigment epithelium (RPE), since RPE injury may be an important feature of age-related macular degeneration (ARMD). METHODS: Retinal cross sections from eyes of Lewis rats were examined for Hsp27 in vivo by immunohistochemistry, and in vitro expression of Hsp27 in human ARPE-19 cells was determined by Northern and Western blot analysis. Oxidant-mediated injury was performed by exposing ARPE-19 cells to myeloperoxidase and hydrogen peroxide. Cell lines stably expressing green fluorescent protein (GFP) targeted to the cell membrane were used to study injury-induced membrane blebbing, and XTT conversion was used to detect cell viability. RESULTS: High level of Hsp27 expression was detected in vivo in ganglion cells, RPE, and photoreceptor outer segments of rat retina. ARPE-19 cells also expressed high levels of Hsp27 in vitro. Oxidative injury in ARPE-19 cells resulted in transcriptional and translational activation of Hsp27 and induced extensive membrane blebbing. A high level of Hsp 27 protein was detected within membrane blebs. Increased expression of Hsp27 was also observed in differentiated ARPE-19 cells when compared with dividing cells. Higher Hsp27 levels in differentiated RPE cells correlated with increased viability and phenotypically different blebbing after exposure to the injury stimulus. In addition, sublethal injury doses caused a moderate amount of membrane blebbing, which was well tolerated by differentiated ARPE-19 cells. CONCLUSIONS: These results indicate that Hsp27 may be an important component of the RPE injury response and may contribute to injury-induced membrane blebbing in differentiated RPE cells. It is hypothesized that Hsp27 levels may play a role in disease states in the retina, such as ARMD.
Animals↗
Intravitreal sustained-release cyclosporine in the treatment of experimental uveitis.
OBJECTIVE: Uveitis often is a chronic disease requiring long-term medical therapy. Despite treatment, the disease may be difficult to control and may produce serious, vision-threatening ocular complications. In this study, the authors determined whether an intravitreal cyclosporine-sustained delivery device was effective in the treatment of ocular inflammation in a rabbit model of uveitis. METHODS: New Zealand White rabbits were immunized subcutaneously with Mycobacterium tuberculosis H37Ra antigen. Fourteen days later, sustained-release cyclosporine devices were implanted into the vitreous cavity of the right eye of experimental rabbits. Control animals received sham devices. Seven days after device implantation, rabbits were challenged with an intravitreal injection of tuberculin antigen. To simulate chronic inflammation with exacerbations, some animals were rechallenged with intravitreal antigen on day 21 after device implantation. Inflammation was assessed clinically by a masked observer who graded anterior chamber cells, flare, corneal neovascularization, iris congestion, and vitreous opacity daily until day 7 and on day 13 after the initial intravitreous challenge, and on days 1 and 2 after the rechallenge. Retinal function was evaluated by electroretinography. Animals were killed 3, 6, 8, and 14 days after the initial intravitreal challenge and on the second day after rechallenge for aqueous leukocyte count, protein measurement, and histologic examination. The number of aqueous and peripheral blood proliferating lymphocytes and the subset of CD4+ T cells were determined by flow cytometry. High-performance liquid chromatography was used to measure cyclosporine A levels in vitreous and peripheral blood. Light microscopy was used to evaluate the eyes histopathologically. RESULTS: By clinical criteria, treated eyes had significantly less inflammation than untreated eyes. The number of aqueous cells and protein concentration determined quantitatively paralleled the clinical assessment of anterior chamber cells and flare. The electroretinography B-wave was depressed significantly in untreated eyes compared with that of treated eyes (P < 0.02). Histopathologic examination results showed marked inflammation and tissue disorganization in untreated eyes, whereas cyclosporine-treated eyes had preserved architecture and greatly reduced inflammatory cells. Intravitreal cyclosporine remained at therapeutic levels for at least 6 months after intravitreal device implantation, whereas blood levels were low to nondetectable. CONCLUSIONS: The intravitreal cyclosporine A device effectively suppresses ocular inflammation in a rabbit model of uveitis. This device may be useful in the treatment of patients with severe chronic uveitis who are intolerant to currently available therapies.
Animals↗
Therapeutic effect of periocular corticosteroids in experimental proliferative vitreoretinopathy.
OBJECTIVE: To test the therapeutic effect of periocular corticosteroid injection on outcome, vitreous cellular infiltrate, and vitreous soluble growth-stimulating activity in an experimental model of tractional retinal detachment resulting from proliferative vitreoretinopathy. METHODS: An experimental model of proliferative vitreoretinopathy was induced in rabbits, which then were selected randomly to receive either periocular methylprednisolone acetate injection treatment or a placebo injection (control). Animals were examined and monitored to determine the degree of retinal detachment and proliferative vitreoretinopathy at weekly intervals for 4 weeks. Vitreous specimens were obtained each week and analyzed for cell number by flow cytometry and for soluble growth-stimulating activity using a bioassay. RESULTS: Eighty-six percent (12 of 14) of the rabbits receiving periocular steroid injection had retinas that remained attached, whereas only 13 percent (2 of 15) of control animals had retinas that remained attached. Periocular steroid injections were associated with a significant decrease in the vitreous soluble proliferation stimulating activity at all times during experimental proliferative vitreoretinopathy. Vitreous cellular infiltration also was reduced significantly in steroid-treated animals compared with that of control animals. Finally, the magnitude of the soluble growth-stimulating activity at day 7, before onset of proliferative vitreoretinopathy, was highly predictive of outcome 3 weeks later. CONCLUSION: Periocular steroids decreased the incidence of complicated retinal detachment caused by proliferative vitreoretinopathy in this rabbit model. Decreased vitreous cellular infiltrate and soluble proliferation stimulating activity within the vitreous microenvironment also was observed to be associated with successful outcome.
Adrenal Cortex Hormones↗
Antibody alone does not prevent experimental cytomegalovirus retinitis in mice with retrovirus-induced immunodeficiency (MAIDS).
Passive-transfer studies were performed to assess the ability of antibody alone to reduce the frequency and/or severity of necrotizing retinitis caused by murine cytomegalovirus (MCMV) in C57BL/6 mice with retrovirus-induced immunodeficiency syndrome (MAIDS). Initial experiments showed a gradual decline in the ability of mice to initiate humoral immunity during the evolution of MAIDS so that neither MCMV-specific IgM nor IgG could be detected during late-stage MAIDS. Passively administered hyperimmune MCMV immunoglobulin, however, could be detected within the serum of mice with MAIDS for at least 9 days after intraperitoneal injection and protected these animals in preliminary experiments from systemic MCMV disease and death when administered 24 h prior to intraperitoneal challenge with a lethal dose of virus. Nonetheless, passive transfer of hyperimmune MCMV serum to mice with MAIDS failed to reduce intraocular MCMV titers, frequency of retinitis, or severity of retinitis when administered 24 h prior to subretinal MCMV inoculation. Whereas whole eyes of MAIDS animals that received normal mouse serum and were injected subretinally with MCMV had an ocular MCMV titer of 4.3 log10 and a frequency of retinitis of 89% (severity score = 55%), whole eyes of antibody-treated mice with MAIDS had an ocular MCMV titer of 4.3 log10 and a frequency of retinitis of 87% (severity score = 57 %). Passive transfer of a neutralizing MCMV-specific monoclonal antibody also failed to reduce the frequency or severity of MCMV retinitis when administered to mice with MAIDS prior to subretinal MCMV inoculation. Our findings suggest that antibody immunotherapy alone will not be effective therapeutically for cytomegalovirus retinitis in patients with AIDS.
Animals↗
Impact of cultures on management decisions following surgical repair of penetrating ocular trauma.
BACKGROUND AND OBJECTIVE: The purpose of this study was to evaluate the utility of routine bacterial and fungal cultures in the diagnosis of endophthalmitis and in the subsequent management of patients following penetrating ocular trauma. PATIENTS AND METHODS: The medical records of 70 consecutive patients with penetrating ocular trauma for whom intraoperative bacterial and fungal cultures had been obtained from the wound, aqueous, vitreous, and/or intraocular foreign body (IOFB) were retrospectively reviewed. The incidences of infection among eyes with and without a clinical diagnosis of infection were compared. A determination as to change in clinical management (change of antibiotic, length of treatment) was made. RESULTS: Twenty of 70 patients (29%) had positive cultures of the wound, aqueous, vitreous, and/or IOFB. Nine (13%) of the 70 patients were diagnosed as having endophthalmitis, based on clinical findings at presentation and during the subsequent clinical course. Seven (78%) of these 9 patients with a clinical diagnosis of endophthalmitis had positive cultures. The remaining 61 eyes showed no evidence of clinically apparent infections, despite positive cultures from 13 eyes (21%). Microbiologic data derived from the culture results influenced the clinical management of all 7 patients with endophthalmitis. Culture results (positive or negative) did not alter clinical decisions in eyes without clinical evidence of infection. CONCLUSION: Bacterial or fungal cultures obtained from the eye in the setting of penetrating trauma often had growth of organisms without clinical signs of infection. Positive culture results directly influenced management decisions in cases with clinically evident endophthalmitis. However, routine intra-operative bacterial cultures did not help to identify patients in whom endophthalmitis would develop, nor did they assist in directing management decisions in eyes without clinical suspicion of infection.
Adolescent↗
Systemic cytokine immunotherapy for experimental cytomegalovirus retinitis in mice with retrovirus-induced immunodeficiency.
PURPOSE: To evaluate and compare the in vivo administration of interleukin-2 (IL-2) or interleukin-12 (IL-12) in the immunotherapy of necrotizing retinitis caused by murine cytomegalovirus (MCMV) in mice with a retrovirus-induced immunodeficiency syndrome (MAIDS). METHODS: Adult C57BL/6 mice with MAIDS of 8 weeks' duration were treated with either a single intramuscular injection of polyethylene glycol-modified human recombinant IL-2 (PEG-IL-2) or multiple intramuscular injections of murine recombinant IL-12; untreated mice with MAIDS received phosphate-buffered saline. Two days later, the left eyes of all mice were inoculated with MCMV by subretinal injection and evaluated at day 6 for intraocular MCMV titers or at day 10 for frequency of necrotizing MCMV retinitis. RESULTS: Infectious MCMV was significantly reduced in whole eyes of PEG-IL-2-treated mice with MAIDS (2.8 log10), but not in whole eyes of IL-12-treated animals (4.4 log10) when compared with whole eyes of untreated animals with MAIDS (4.5 log10). Similarly, whereas eyes from approximately 80% of IL-12-treated and untreated mice with MAIDS showed histopathologic features consistent with classic necrotizing MCMV retinitis (full-thickness retinal necrosis associated with virus inclusions and cytomegalocytes), none (0%) of PEG-IL-2-treated animals with MAIDS showed classic MCMV retinitis. Instead, eyes from these animals showed either retinal folding or outer retinal atrophy, a pattern of histopathology similar to that observed in eyes from immunologically normal C57BL/6 mice inoculated subretinally with MCMV. CONCLUSIONS: These results provide proof-of-principle for the hypothesis that systemic cytokine immunotherapy will reduce the frequency of CMV retinitis in a setting of retrovirus-induced immunosuppression. Because of the striking differential effects of IL-2 and IL-12 on MCMV-retinitis in mice with MAIDS, the authors conclude that cytokine immunotherapy for cytomegalovirus-induced retinitis is cytokine-specific, even for such cytokines as IL-2 and IL-12 that have T cell regulation in common.
Animals↗
Endophthalmitis after penetrating trauma. Risk factors and visual acuity outcomes.
PURPOSE: To identify clinical characteristics that were associated with an increased incidence of endophthalmitis in eyes with penetrating ocular trauma. METHODS: In part 1, a retrospective analysis was performed on 258 consecutive patients with penetrating ocular trauma presenting to the Bascom Palmer Eye Institute between October 1987 and January 1991. In part 2 of the study, 28 consecutive patients with culture-proven endophthalmitis were identified from the Clinical Microbiology Registry from April 1987 through September 1987 and February 1991 through August 1993. Clinical variables were evaluated in each part for association with an increased risk of endophthalmitis. RESULTS: In part 1 of the study, endophthalmitis developed in 13 (5%) of the 258 patients. Endophthalmitis did not occur in eyes that had blunt injury. In those eyes with a lacerating injury, there was an increased relative risk of infection in eyes with disruption of the crystalline lens. This risk factor was found statistically significant by univariate and multivariate analysis. In part 2 of the study, lens disruption was present in 24 (86%) of 28 patients with culture-proven endophthalmitis. Of the 41 patients with infection from part I and part II, 22 (54%) achieved visual acuity of 20/ 400 or greater. Endophthalmitis caused by coagulase-negative staphylococci had the best visual outcome, with 7 (64%) of 11 patients obtaining visual acuity of 20/ 400 or greater. CONCLUSION: Lens disruption in eyes with penetrating trauma is a significant risk factor for the development of endophthalmitis. The prognosis for useful vision in eyes with posttraumatic endophthalmitis is best when infection is caused by less virulent organisms.
Anti-Bacterial Agents↗
Immunoreactive vasoactive intestinal peptide contributes to the immunosuppressive activity of normal aqueous humor.
Suppression of immune-mediated inflammation within the normal anterior chamber (AC) of the eye is in part the result of active suppression of effector T cell activities by immunosuppressive cytokines found in aqueous humor (AqH), the fluid filling the AC. There are immunosuppressive factors found in the low m.w. fraction (< 5 kDa) of AqH, including the neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH). In seeking other factors, we now report that the neuropeptide vasoactive intestinal peptide (VIP) is also present in normal AqH. VIP immunoreactivity was found in normal rabbit eyes at a concentration of 12 +/- 1 nM. At this intraocular concentration, VIP suppressed Ag-stimulated lymph node cell (LNC) proliferation and IFN-gamma production in vitro. Although suppression of LNC proliferation was not neutralized by absorption of VIP from the low m.w. fraction of AqH, removal of VIP did neutralize suppression of IFN-gamma production by this fraction of AqH. Absorption of both VIP and alpha-MSH from this fraction of AqH permitted production of IFN-gamma by Ag-stimulated LNC that was no different than absorbing VIP alone. The low m.w. fraction of AqH absorbed of either alpha-MSH and VIP lost its ability to suppress local adoptive transfer of delayed-type hypersensitivity. The results suggest that VIP is an important immunosuppressive neuropeptide in AqH. Neuropeptides play an important role in ocular immune privilege and creation of an intraocular immunosuppressive microenvironment.
Animals↗
Prevention of experimental proliferative vitreoretinopathy with a biodegradable intravitreal implant for the sustained release of fluorouracil.
OBJECTIVE: To test the efficacy of a biodegradable device for the intravitreal sustained release of fluorouracil in the treatment of tractional retinal detachment due to proliferative vitreoretinopathy. METHODS: A 6 x 0.9-mm (20-gauge) cylindrical solid implant molded from copolymers of lactide and glycolide admixed with 1 mg of fluorouracil was placed in the vitreous cavity of rabbits in which retinal detachment with proliferative vitreoretinopathy had been initiated. Comparisons of the control (drug-free polymer) and experimental (fluorouracil polymer) groups were made with weekly indirect ophthalmoscopic examinations. In another experiment, the intravitreal concentration of fluorouracil was tested at each time point. RESULTS: Retinas of eight (89%) of nine rabbits that received the polymer with fluorouracil remained attached compared with only one animal (11%) that received the control polymer without the drug. The therapeutic effect of the drug-containing implant was associated with sustained intravitreal concentrations of fluorouracil between 1 and 13 mg/L for at least 14 days, and fluorouracil concentrations remained above 0.3 microgram/mL for almost 21 days. No evidence of the toxic effects of the drug or polymer implant was observed with electroretinographic and histopathologic study. CONCLUSION: Intravitreal implantation of biodegradable polymers containing fluorouracil can prevent proliferation of epiretinal membranes resulting in complicated retinal detachment in an animal model of proliferative vitreoretinopathy and indicate their possible usefulness for intravitreal delivery of therapeutic agents.
Animals↗
Comparison of flow cytometry with the surgeon regarding ability to predict the ultimate success of surgery for proliferative vitreoretinopathy.
OBJECTIVE: To analyze vitreous specimens obtained from human eyes with proliferative vitreoretinopathy (PVR) by use of flow cytometery (FC) to compare the capacity of FC with that of the surgeon's in predicting the ultimate outcome after PVR surgery. METHODS: Thirty-one vitreous aspirates were obtained at vitrectomy or from postoperative fluid-gas exchanges for complicated retinal detachment due to PVR. Samples were analyzed by FC for the concentration of total and proliferating cells. These measurements were compared with the surgeon's preoperative prognosis (good, poor, or indeterminate) for the ultimate result. At 12 weeks, the eyes were evaluated for clinical outcome. An unsuccessful outcome was one in which the retina was attached with macular pucker or hypotony or was anatomically detached. Anatomic attachment of the retina anterior and posterior to the scleral buckle without these findings was considered a successful outcome. RESULTS: Flow cytometry was capable of quantifying the concentration of total and proliferating cells in eyes with PVR. Eyes destined for an ultimately successful outcome demonstrated fewer total and proliferating cells than did eyes destined for an unsuccessful outcome. No differences were observed between eyes destined for development of macular pucker and those destined for anatomic redetachment. The surgeon was able to accurately predict a good or a poor outcome in 64.5% of the cases, with a sensitivity of 92% and a specificity of 89%. Using the total number of recovered cells, FC was able to correctly predict a good or a bad outcome with a 77% accuracy, whereas the surgeon was able to do so with a 65% accuracy. Combining the surgeon's prediction with the result of FC increased the diagnostic power of the prediction to 87%. CONCLUSIONS: The diagnostic power of FC was similar to that of the surgeon's in predicting ultimate outcome, but the two techniques probably evaluate different features of the disease process. The combination of the two techniques was the most powerful approach to the prediction of ultimate outcome after PVR surgery.
Cell Count↗
Diagnostic ultrasound and pars plana vitrectomy in penetrating ocular trauma.
PURPOSE: The purpose of this study is to evaluate the accuracy of diagnostic ultrasonography in the preoperative evaluation of eyes with media opacity after penetrating ocular trauma and correlate the preoperative findings with ultimate visual outcome. METHODS: A retrospective comparison was made between the preoperative ultrasound diagnoses and the intraoperative findings in 46 eyes of 45 patients undergoing pars plana vitrectomy after penetrating ocular trauma associated with dense media opacities. The preoperative echographic findings were correlated with long-term visual and anatomic outcome. RESULTS: Preoperative echography was both sensitive and specific in evaluating traumatized eyes for retinal detachment, intraocular foreign bodies, posterior scleral wounds, and hemorrhagic choroidal detachments. The overall anatomic success rate was 87% (40/46) with 48% (22/46) of eyes obtaining visual acuity of 20/200 or better after surgery. The visual prognosis was worse in those eyes in which preoperative echography detected retinal detachment, subretinal blood, massive choroidals, or posterior exit wounds. CONCLUSION: Diagnostic echography is accurate and provides useful prognostic information in eyes with media opacity after penetrating ocular trauma.
Choroid Hemorrhage↗
Mice immunosuppressed by murine retrovirus infection (MAIDS) are susceptible to cytomegalovirus retinitis.
Although various methods of immunosuppression have been used to enhance susceptibility of mice to murine cytomegalovirus (MCMV) retinitis, none reproduce the unique complexity of immune deficiency experienced by patients during the progression of AIDS. C57BL/6 mice are susceptible to a retrovirus-induced murine acquired immune deficiency syndrome (MAIDS), characterized by progressive immune dysfunction which shares many features with AIDS. We therefore evaluated the frequency and severity of MCMV retinitis in C57BL/6 mice with MAIDS. Following subretinal inoculation of MCMV, nearly 90% of mice with MAIDS developed a necrotizing retinitis 8 to 10 days postinfection, whereas retinitis was observed in only 8% of age-matched immunocompetent control mice. Histopathologic analysis of the retinitis that developed in mice with MAIDS revealed features similar to those found in AIDS-related CMV retinitis. Eyes from MAIDS animals also contained on average higher amounts of infectious virus when compared with eyes from control animals. We conclude that retrovirus-induced immunosuppression increases susceptibility of C57BL/6 mice to MCMV retinitis.
Animals↗
Modulation of murine herpes simplex virus type 1 retinitis in the uninoculated eye by CD4+ T lymphocytes.
PURPOSE: To investigate the contribution of CD4+ and CD8+ T lymphocytes to retinitis in the contralateral eye after anterior chamber inoculation of herpes simplex virus type 1 (KOS strain). METHODS: T-cell-depleted BALB/c mice were prepared by adult thymectomy and treatment with anti-L3T4 (anti-CD4) monoclonal antibody and/or anti-Lyt2.2 (anti-CD8) monoclonal antibody. On days 9 and 14 after inoculation of herpes simplex virus type 1 (KOS strain) via the anterior chamber, the titer of virus in the uninoculated eye was determined by plaque assay. The eyes were examined microscopically, and the severity of retinitis was evaluated using a histopathologic scoring system. RESULTS: At day 14 postinoculation, significantly less severe destruction of the parenchyma and less inflammatory cell infiltration were observed in the retina of the uninoculated eye of CD4+ T-cell-depleted mice and of mice depleted of both T-cell subsets. The titer of virus in the uninjected eye of CD4+ T-cell-depleted mice and of mice depleted of both CD4+ and CD8+ T cells was also significantly higher at day 14 postinoculation. CONCLUSIONS: The results of the studies suggest three ways CD4+ T cells might contribute to the pathogenesis of herpes simplex virus type 1 retinitis in the uninoculated contralateral eye: (1) accumulation of massive inflammatory cell infiltrates in the retina, (2) induction of retinal destruction, and (3) clearance of herpes simplex virus type 1 from the contralateral eye. In infection of the contralateral retina of nondepleted mice after uniocular anterior chamber inoculation of KOS, CD4+ T cells are required to induce fulminant retinitis and to mediate clearance of virus from the uninoculated eye by day 14 postinoculation. The exact mechanism by which CD4+ T cells contribute to contralateral retinitis remains to be identified.
Animals↗
Measurement of cellular proliferation within the vitreous during experimental proliferative vitreoretinopathy.
Cellular proliferation is an important component in the pathogenesis of complex retinal detachments caused by proliferative vitreoretinopathy (PVR). We used flow cytometry to measure the proliferation of cells recovered from the vitreous cavity in an experimental model of tractional retinal detachment induced by homologous fibroblast injection. Two distinct populations of cells were detected. One population comprised smaller, dense cells representing mostly leukocytes. A second population of larger cells contained not only the injected fibroblasts but also high concentrations of host-derived cells with significant proliferative activity, whose number increased for 3 days following injection. Flow cytometry was useful for analysis of the recovered cells for concentration, morphologic features and proliferation. This technique may be applicable in the identification of patients at high risk for the development of PVR.
Animals↗
Immunoregulatory mechanisms of the eye.
Immune-privileged sites, such as the the internal compartments of the eye, and perhaps the brain, are physiological adaptations that act to modify systemic immune responses such that effector mechanisms that invoke locally destructive inflammation are suppressed. In the case of the eye, the parenchymal cells of the iris and ciliary body create an intraocular microenvironment that alters both the induction and expression of immunity to antigens placed within the eye. The immunosuppressive properties of the intraocular microenvironment are mediated by cytokines, especially transforming growth factor-beta (TGF beta). This cytokine has been demonstrated to endow intraocular antigen-presenting cells with the capacity to induce an atypical or deviant form of immunity to intraocular antigens which is selectively deficient in T cells that mediate delayed hypersensitivity. Moreover, TGF beta, along with other intraocular factors, can impair the intraocular expression of pre-existing cell-mediated immunity by inhibiting antigen-driven activation of primed T cells. The strategies employed by the eye to engender specialized immune responses appropriate to its physiological functions are discussed in terms of other privileged sites such as the brain.
Animals↗