Graft-Versus-Host Disease Following Liver Transplantation: Development of a High-Incidence Rat Model and a Selective Prevention Method.

Graft-versus-host disease (GvHD) following liver transplantation (LT) is a rare but serious complication with no presently available animal model and no preventive measures. To develop a rat model of GvHD after LT (LT-GvHD), we preconditioned hosts with sublethal irradiation plus reduction of natural killer (NK) cells with anti-CD8α mAb treatment, which invariably resulted in acute LT-GvHD. Compared with those in the peripheral counterpart, graft CD4+ CD25- passenger T cells showed lower alloreactivities in mixed leukocyte culture. Immunohistology revealed that donor CD4+ T cells migrated and formed clusters with host dendritic cells in secondary lymphoid organs, with early expansion and subsequent accumulation in target organs. For selectively preventing GvHD, donor livers were perfused ex vivo with organ preservation media containing anti-TCRαß mAb. T cell-depleted livers almost completely suppressed clinical GvHD such that host rats survived for >100 days. Our results showed that passenger T cells could develop typical LT-GvHD if resistant cells such as host radiosensitive cells and host radioresistant NK cells were suppressed. Selective ex vivo T cell depletion prevented LT-GvHD without affecting host immunity or graft function. This method might be applicable to clinical LT in prediagnosed high-risk donor-recipient combinations and for analyzing immunoregulatory mechanisms of the liver.

Travoprost 0.004%/timolol 0.5%-fixed combination with and without benzalkonium chloride: a prospective, randomized, doubled-masked comparison of safety and efficacy.

PURPOSE: The purpose of this study is to compare the safety and intraocular pressure (IOP)-lowering efficacy of travoprost/timolol in a benzalkonium chloride (BAK)-free fixed combination preserved with polyquaternium-1 (TRA/TIM BAK-free), with travoprost/timolol-fixed combination preserved with BAK (TRA/TIM), in patients with open-angle glaucoma or ocular hypertension. METHODS: In this prospective randomized controlled trial, subjects with IOP of at least 22 mm Hg in one or both eyes at 0900 h, and IOP of at least 21 mm Hg in one or both eyes at 1100 h and 1600 h at two eligibility visits were randomly assigned to receive either TRA/TIM BAK-free (n=195) or TRA/TIM (n=193), dosed once daily in the morning (0900 h) for 6 weeks. IOP was assessed at 0900 h, 1100 h, and 1600 h at each scheduled visit (baseline, 2 and 6 weeks after randomization). RESULTS: Mean IOP reduction across all visits and time points was 8.0 mm Hg in the TRA/TIM BAK-free group and 8.4 mm Hg in the TRA/TIM group (P=0.0943). The difference in mean IOP between groups ranged from 0.2 to 0.7 mm Hg across visits and time points, with a mean pooled difference of 0.4 mm Hg (95% CI: -0.1 to 0.8), demonstrating equivalence of the two formulations. The most common drug-related adverse event was hyperemia of the eye (ocular hyperemia and conjunctival hyperemia combined), occurring in 11.8% of the TRA/TIM BAK-free group and 13.0% of the TRA/TIM group. CONCLUSION: Travoprost/timolol BAK-free demonstrated equivalence to travoprost/timolol preserved with BAK in efficacy. No clinically relevant differences in the safety profiles of travoprost/timolol BAK-free and travoprost/timolol preserved with BAK were identified.

PD-1/B7-H1 interaction contribute to the spontaneous acceptance of mouse liver allograft.

The programmed death-1 (PD-1)/B7-H1 pathway acts as an important negative regulator of immune responses. We herein investigated the role of the PD-1/B7-H1 pathway in establishing an immunological spontaneous tolerance status in mouse liver allografting. B7-H1 is highly expressed on the donor-derived tissue cells and it is also associated with the apoptosis of infiltrating T cells in the allografts. Strikingly, a blockade of the PD-1/B7-H1 pathway via anti-B7-H1mAb or using B7-H1 knockout mice as a donor led to severe cell infiltration as well as hemorrhaging and necrosis, thus resulting in mortality within 12 days. Furthermore, the expression of the FasL, perforin, granzyme B, iNOS and OPN mRNA in the liver allografts increased in the antibody-treated group in comparison to the controls. Taken together, these data revealed that the B7-H1 upregulation on the tissue cells of liver allografts thus plays an important role in the apoptosis of infiltrating cells, which might play a critical role of the induction of the spontaneous tolerance after hepatic transplantation in mice.

Population-based prevalence of optic disc haemorrhages in elderly Japanese.

PURPOSE: To estimate the population-based prevalence of disc haemorrhages (DHs) in an elderly Japanese population and evaluate related factors including optic disc morphology. PATIENTS AND METHODS: Colour fundus photographs were taken during the screening examination of the Tajimi Study, during which 3021 of 3870 eligible residents of the city aged 40 years or older were screened (response rate, 78.1%). All fundus photographs were graded by one masked examiner to determine the presence of DHs. RESULTS: Good quality fundus photographs were available for both eyes of 2761 subjects. DHs were found in at least one eye of 34 subjects (1.2%; 95% confidence interval (CI) 0.8-1.6%). The prevalence was 14.0% (95% CI, 8.0-19.9%), 9.7% (2.9-16.6%), and 0.4% (0.1-0.6%) in subjects with definitive glaucoma, glaucoma suspects, and subjects without glaucoma, respectively. Logistic regression analyses indicated that DHs were associated with glaucoma (P<0.001), glaucoma suspects (P<0.001), and older age (P=0.032). No Heidelberg Retina Tomograph parameters differed between subjects with and without DHs. CONCLUSIONS: The prevalence of DHs was 1.2% in an elderly Japanese population, which was similar to other population studies. In addition to glaucoma, older age was associated with higher prevalence of DHs.

Superagonistic CD28 antibody induces donor-specific tolerance in rat renal allografts.

The ultimate goal of organ transplantation is to establish graft tolerance where CD4+CD25+FOXP3+ regulatory T (Treg) cells play an important role. We examined whether a superagonistic monoclonal antibody specific for CD28 (CD28 SA), which expands Treg cells in vivo, would prevent acute rejection and induce tolerance using our established rat acute renal allograft model (Wistar to Lewis). In the untreated or mouse IgG-treated recipients, graft function significantly deteriorated with marked destruction of renal tissue, and all rats died by 13 days with severe azotemia. In contrast, 90% of recipients treated with CD28 SA survived over 100 days, and 70% survived with well-preserved graft function until graft recovery at 180 days. Analysis by flow cytometry and immunohistochemistry demonstrated that CD28 SA induced marked infiltration of FOXP3+ Treg cells into the allografts. Furthermore, these long-surviving recipients showed donor-specific tolerance, accepting secondary (donor-matched) Wistar cardiac allografts, but acutely rejecting third-party BN allografts. We further demonstrated that adoptive transfer of CD4+CD25+ Treg cells, purified from CD28 SA-treated Lewis rats, significantly prolonged allograft survival and succeeded in inducing donor-specific tolerance. In conclusion, CD28 SA treatment successfully induces donor-specific tolerance with the involvement of Treg cells, and thus the therapeutic value of this approach warrants further investigation and preclinical studies.

Exogenous expression of Fas-ligand or CrmA prolongs the survival in rat liver transplantation.

Modulation of donor organs by transfection of a gene encoding immmunosuppresive molecules has been recognized as a less toxic approach to prevent allograft rejection. Fas-ligand (FasL) plays a critical role in activation-induced cell death of activated cytotoxic lymphocytes. This may provide a potential for induction of "immune privileged sites" to escape the host immune surveillance system. Cytokine response modifier A (CrmA), a gene product of cowpox virus, blocks caspase as well as perforin/granzyme-mediated apoptotic pathways. Therefore, it may suppress intragraft apoptosis. The aim of the present study was to investigate whether transfection of FasL or CrmA genes prolonged the survival of rat liver allografts. Using the high responder rat combination of DA (RT-1(a)) donor to LEW (RT-1(1)) recipient, we performed orthotopic liver transplantation with subsequent delivery of adenoviral vectors containing FasL, CrmA, or LacZ, at a dose of 1 x 10(9) pfu via a recipient tail vein using a Cre-mediated gene expression system. Recipient survival was assessed as well as immunohistochemical examination of the grafts for anti-CD2, TUNEL, and H&E staining. Statistical analysis was performed with the Mann-Whitney U test. The therapeutic groups showed significantly prolonged recipient survival compared with the LacZ-treated control group. Histologic analysis revealed reduced hepatocyte apoptosis in the CrmA-treated group and increased apoptosis of infiltrating mononuclear cells in the FasL-treated group. These data suggested that FasL and CrmA may be potent genes to prolong rat liver allograft survival.

Return to home early days after acute aortic dissection surgery.

AIM: The length of hospital stay after acute aortic dissection surgery tends to be prolonged. The aim of this study is to assess the feasibility of our protocol for early discharge after acute aortic dissection surgery. METHODS: This study enrolled 17 consecutive acute aortic dissection patients who returned to their own home within 2 weeks of surgery. In seven patients total aortic arch replacement was performed and in 7 partial arch replacement. The main aim of the first 24 h after surgery was to achieve early extubation. Patients were encouraged to return to their own home 4 days and later after surgery. The prerequisite criteria for discharge were the following: independent mobility, stable hemodynamics, apyrexia, adequate oral intake, normal bowel function, healthy surgical wound and the patient's agreement for discharge. RESULTS: The mean age of these patients was 59. The postoperative ventilation time, length of intensive care unit stay and postoperative hospital stay were 11 h, 37 h and 6.9 days, respectively. Two (12%), 13 (76%) and 14 (82%) patients returned to their own home by postoperative day 4, 7 and 10, respectively. Three patients were readmitted to a peripheral hospital in the 4 week postoperative period. The reason for all readmissions was lack of family support. Two other patients underwent pericardiocentesis for pericardial effusion at an other hospital as outpatients. There was no complication caused by early discharge. CONCLUSIONS: Early discharge after aortic dissection surgery is safe and recommended to patients who have normal bowel function and adequate family support.

Optic disc topographic parameters measured in the normal cynomolgus monkey by confocal scanning laser tomography.

AIM: To study optic disc topographic parameters in normal cynomolgus monkeys by Heidelberg retina tomograph (HRT). METHODS: 12 optic disc topographic parameters were investigated in 36 normal eyes in 18 male monkeys. Mean (SD) and interocular differences were obtained for each parameter from three independent measurements made during a 1 week period. Correlations among the topographic parameters were analysed, too. RESULTS: No significant differences between right and left eyes were detected for any topographic parameters. Disc area, rim area, and height variation contour showed smaller right-left differences than other parameters. The coefficients of variation for rim area, height variation contour, rim volume, mean cup depth, maximum cup depth, mean retinal nerve fibre layer (RNFL) thickness, and RNFL cross section area were less than 10% (for rim area, less than 5%). Rim area and height variation contour showed relatively weak interrelations and neither showed a correlation with disc area. CONCLUSION: For evaluating time related changes in the optic disc by HRT in monkeys, rim area and height variation contour might be useful parameters because coefficients of variation and right-left differences were lower than for other parameters and because these parameters showed weak interrelations and no correlation with disc area.

A three-year prospective, randomized and open comparison between latanoprost and timolol in Japanese normal-tension glaucoma patients.

PURPOSE: To compare the longitudinal effects of treatment on intraocular pressure (IOP) and visual field performance in Japanese normal-tension glaucoma (NTG) between latanoprost and timolol. PATIENTS AND METHODS: This is an open-label, randomized, study. A total of 62 NTG patients were prospectively, consecutively enrolled. All study subjects were randomly assigned to 0.005% latanoprost instillation once daily in the morning or 0.5% timolol instillation twice daily for a prospective 3-year follow-up, and underwent a routine ocular examination every month. Automated perimetry was performed every 6 months using Humphrey field analysers. Stereophotographs of optic discs were also obtained every 6 months. RESULTS: Percentage of IOP reduction or the magnitude of IOP reduction showed no intergroup differences either at any time point (13-15%). In the visual field, the estimated rate of change in the MD value (dB/year) was -0.34+/-0.17 (SE) for the latanoprost group, and -0.10+/-0.18 (SE) for the timolol group. The estimated rate of change in MD showed no significant difference from zero in both groups, and there were no statistical intergroup differences. No changes in the optic nerve head topography in the vertical cup-to-disc ratio and rim area measured by image-analysis techniques were observed in either group. There were no patients who dropped out due to the side effects of treatment regimens. CONCLUSION: Both latanoprost and timolol single treatments reduced IOP by 13-15% at their trough effects for 3 years in Japanese NTG patients; both showed similar effects on visual field performance.

CrmA gene expression protects mice against concanavalin-A-induced hepatitis by inhibiting IL-18 secretion and hepatocyte apoptosis.

Activated cytotoxic T-cell-mediated hepatocyte apoptosis via Fas/Fas-ligand and perforin/granzyme pathways are believed to involve the model of concanavalin A (ConA)-induced hepatitis. The purpose of the present study is to investigate whether the cytokine response modifier A (crmA) gene effectively inhibits the hepatocyte apoptosis of ConA-induced hepatitis. We examined survival rates, liver pathology, immune histological changes, and cytokine profiles from mice receiving the recombinant adenovirus vectors containing cre and/or crmA genes, transferred to the liver 3 days before ConA injection, and a crmA gene nonexpression control group. Injection of ConA into mice rapidly led to massive hepatocyte apoptosis, and infiltration of leukocytes, especially CD11b(+) inflammatory cells. In contrast, liver damage was dramatically reduced in the mice that expressed the crmA gene. However, infiltration by CD4(+) cells was not affected. The survival of the mice increased significantly to 100% in the treated group versus the control group. Furthermore, we demonstrated that interleukin (IL)-18 plays an important role in ConA-induced hepatitis, and that crmA expression significantly inhibited IL-18 secretion. Our results showed that the crmA gene effectively inhibits apoptosis induced by ConA hepatitis. This indicates a potential therapeutic usage of crmA for protection from cellular damage due to hepatitis.

Screening for mutations of Axenfeld-Rieger syndrome caused by FOXC1 gene in Japanese patients.

PURPOSE: Mutations in the forkhead transcription factor gene (FOXC1) have been recently shown to cause some cases of juvenile glaucoma associated with a variety of anterior-segment anomalies. The purpose of this study was to investigate the clinical features of Axenfeld-Rieger syndrome caused by FOXC1 mutations in Japanese patients. PATIENTS AND METHODS: After informed consent was obtained, genomic DNA was isolated from peripheral blood. The DNA-sequence changes were analyzed using single-strand conformation polymorphism analysis and automated sequencing in six Japanese probands with Axenfeld-Rieger syndrome. RESULTS: The authors identified four mutations: pedigree 1 (26-47ins22), 2 (Ile91Ser), 3 (286ins1), and 4 (Arg127His). Two pedigrees showed new mutations in FOXC1. In pedigrees 1,2, and 4, younger generations had iris hypoplasia with severe early-onset glaucoma, whereas their parents had posterior embryotoxon without glaucoma. Pedigree 3 had a single affected person with iris hypoplasia and posterior embryotoxon with a mild increase of intraocular pressure. CONCLUSION: Four different FOXC1 mutations were found in four of six Japanese pedigrees with Axenfeld-Rieger syndrome. This was a new mutation in two pedigrees that was not found in earlier generations. This study confirms that mutations in this gene cause maldevelopment of the anterior segment of the eye.

Morphometric characteristics of optic disk with disk hemorrhage in normal-tension glaucoma.

PURPOSE: To evaluate the morphometric characteristics of the optic disk in eyes with and without disk hemorrhage in normal-tension glaucoma. METHODS: This was a prospective study conducted at Gifu University Hospital of 50 eyes of 50 patients with normal-tension glaucoma (12 men, 38 women; age, 56.5 +/- 14.1 years) who had developed new disk hemorrhage at the time of enrollment and 58 eyes of 58 patients with normal-tension glaucoma (20 men, 38 women; age, 56.7 +/- 12.4 years) with no history of disk hemorrhage during the follow-up period of more than 2 years. Age and global indexes of the visual field were matched. We morphometrically compared the optic disk with and without hemorrhage using a scanning laser tomograph. Global and sector analyses were made of the optic disk structural parameters. RESULTS: There was no significant difference in the global values of the disk parameters between the disk hemorrhage and the nonhemorrhage groups. However, the inferotemporal values for the rim area, rim volume, mean retinal nerve fiber layer thickness, and retinal nerve fiber layer cross-section area in the disk hemorrhage group were significantly smaller than those in the nonhemorrhage group (P <.05). In the disk hemorrhage group, moreover, the values for the rim area, rim volume, and retinal nerve fiber layer cross-section area in the inferotemporal sector with hemorrhage were significantly smaller than those in the same sector without hemorrhage (P <.05). CONCLUSION: Localized damage of the disk rim and retinal nerve fiber layer at the inferotemporal sector was prominent in eyes with disk hemorrhage.

Selective repopulation of mice liver after Fas-resistant hepatocyte transplantation.

Hepatocyte transplantation has been proposed as a potential therapeutic method to treat irreversible liver failure and inherited hepatic disorders, although transplanted cells do not easily reconstruct the liver tissue under intact conditions. This study was aimed at modulating the recipient liver conditions to promote repopulation of the liver after hepatocyte transplantation. Hepatocytes isolated from male MRL-lpr/lpr (lpr) mice with a mutation of Fas antigen were transplanted in a number of 1 x 10(6) cells in female MRL-+/+ (wild-type mice) by intrasplenic injection. An agonistic anti-Fas antibody (0.15 mg/kg) was administered intravenously 24 h after cell transplantation. We also administrated the antibody at 0.3 mg/kg 1 week after grafting and at 0.6 mg/kg 2 weeks after transplantation. The liver specimens were taken at different time intervals for histological examination. The reconstructed male lpr hepatocytes in the female wild-type mice were determined by a real-time quantitative PCR assay using the primers and probe for the sry gene. The pathologic findings of the recipient livers after treatment with anti-Fas antibody revealed a large number of apoptotic hepatocytes. The grafted lpr hepatocytes were observed to reconstruct as much as 6.9% of the recipient liver in the anti-Fas antibody-treated group 3 months after transplantation. In contrast, we observed the transplanted cells at lower than 0.1% in the nontreated livers. These findings demonstrated that repeated induction of apoptosis in recipient hepatocytes shifts the environment of the liver to a regenerative condition. This method may be useful to promote the reconstruction of transplanted hepatocytes in a recipient liver.

Intraocular pressure-lowering efficacy of latanoprost in patients with normal-tension glaucoma or primary open-angle glaucoma.

We investigated the intraocular pressure (IOP)-lowering potential of latanoprost in patients with normal-tension glaucoma (NTG) or primary open-angle glaucoma (POAG). This prospective study included 59 NTG and 20 POAG patients treated with the following four dosing regimens of latanoprost: patients on no previous medication received latanoprost as initial therapy (Group 1, n=31), patients on beta-blocker therapy received latanoprost as adjunctive therapy (Group II, n=9), patients on unoprostone monotherapy were switched to latanoprost monotherapy (Group III, n=14), and patients previously on dual therapy with isopropyl unoprostone and beta-blocker were switched to a combined treatment of latanoprost and beta-blocker (Group IV, n=25). IOP significantly decreased 8 weeks after initiation of latanoprost therapy by 19.9% in Group I, 20.5% in Group II, 16.6% in Group III, and 12.2% in Group IV. In Groups I and II, there was a significant positive correlation between the magnitude of IOP reduction induced by latanoprost and the IOP level before latanoprost therapy. The IOP level before latanoprost therapy is a contributing factor in the IOP-lowering efficacy of latanoprost. Latanoprost is more effective in lowering IOP than isopropyl unoprostone.

Respiratory and cardiovascular effects of WP-934 in guinea pigs.

WP-934 is a newly developed reversible thermo-setting in situ gelling ophthalmic solution containing timolol. We investigated the effects of WP-934 on the respiratory and cardiovascular systems in guinea pigs and compared them with those of the conventional ophthalmic solution of timolol. At 30 min after instillation of timolol 0.5%, the airway responsiveness to histamine was 4 times higher, and that to acetylcholine was 2.5 times higher, than that before instillation. At 30 min after instillation of WP-934 0.5%, in contrast, the increase in responsiveness to each drug was about half that seen with the conventional solution. Topical instillation of timolol 0.5% weakened the effects of salbutamol and aminophylline on bronchodilatation, while that of WP-934 0.5% had no effect on aminophylline-induced bronchodilatation and a weaker effect on salbutamol-induced bronchodilatation. Topical instillation of timolol 0.5% and WP-934 0.5% failed to show a significant effect on blood pressure but caused a 10 to 20% decrease in heart rate for at least 120 min after instillation. WP-934 appears to have less respiratory adverse effects than timolol, mainly due to its longer retention on the ocular surface and a consequent decrease in systemic absorption.

[Blood flow in retinal vessels of normal-tension glaucoma with or without a history of optic disc hemorrhages].

PURPOSE: To evaluate blood flow in retinal vessels of normal-tension glaucoma (NTG) with or without a history of optic disc hemorrhages (DH) and compare it with that in non-glaucomatous eyes using scanning laser fluorescein video angiography. METHODS: We enrolled 14 eyes of 14 NTG patients with a history of DH (DH (+) group), 12 eyes of 12 NTG patients without history of DH (DH (-) group), and 10 eyes from 10 non-glaucomatous patients matched for age, intraocular pressure, and systemic blood pressure. No statistically significant difference was observed between the DH (+) and DH (-) groups of NTG in the global indices of the Humphrey visual field. Fluorescein angiography was performed using a scanning laser ophthalmoscope with an argon blue laser. A series of approximately 100 consecutive video images at 1/2 second intervals from just before the dye appearance in the central retinal artery was loaded into an external personal computer system. Based on this acquired image series, we obtained fluorescein filling curves for 10 x 10 pixel measuring areas placed on each of the superior-temporal and inferior-temporal branch retinal arteries and veins at 1/5 papillary diameter from the disc edge. In each vessel, time to the highest fluorescein intensity (peak time, sec) and the time constant of the filling curve (tau, sec) were obtained. Time difference between the peak times in vein and artery (peak time difference) was also calculated. RESULTS: Statistically significant differences were observed among the three groups in the peak time of inferior-temporal artery and vein, and superior-temporal vein (ANOVA, p < 0.01). Also there were statistically significant differences in the tau of all vessels (ANOVA, p < 0.05). No statistically significant differences were observed in the peak time differences. By multivariate analysis, the DH (+) and DH (-) groups of NTG showed significantly longer peak times and tau s than did the non-glaucomatous eyes (p < 0.05). However, no statistically significant differences were observed in any parameters between the DH (+) and DH (-) groups of NTG. CONCLUSIONS: In NTG, dye filling rate in both the central retinal arteries and veins seems to be delayed. However, this delay does not differ between DH (+) and DH (-) groups.

Mathematical and optimal clustering of test points of the central 30-degree visual field of glaucoma.

PURPOSE: To determine a mathematically optimal sector pattern of the central 30 degree visual field for the follow-up of glaucomatous visual field change based on a large number of actual visual field test data of patients with glaucoma. METHODS: Visual field test data obtained from 1,039 eyes of 1,039 patients with open-angle glaucoma (OAG) using the 30-2 program of the Humphrey Field Analyzer were used for sectorization of the central 30 degree visual field. Of the 1,039 visual field data, 698 (modeling data) were used for determining the sector pattern and 341 (testing data) for checking the sector pattern. The modeling data were further divided into three groups according to the mean deviation (MD) (MD > or = -10 dB, -20 < or = MD < -10 dB, and MD < -20 dB), and the sector pattern was constructed from visual field data of each group using a clustering procedure called VARCLUS. The testing data were used for determining the optimal sector pattern. In a separate set of repeated visual field data of 303 patients with OAG, the fluctuation of MD, sector values of each sector determined, and total deviation of each test point were calculated and compared. RESULTS: The sector pattern constructed from visual field data of MD > or = -10 dB summarized the visual field performance most effectively. The fluctuation of the sector value of each sector was roughly 1.5 times smaller than the total deviation of each test point. CONCLUSION: The sector pattern determined may be useful in analyses of the visual field data of patients with glaucoma.

Serum autoantibodies to heat shock proteins in glaucoma patients from Japan and the United States.

OBJECTIVE: To study serum titers of antibodies against heat shock proteins in glaucoma patients from two different ethnic populations and to examine the relationship between serum antibody titers and glaucomatous damage. STUDY DESIGN: Comparative, cross-sectional study. PARTICIPANTS: Twenty-seven age-matched patients with primary open-angle glaucoma, 28 patients with normal pressure glaucoma, and a control group of 26 healthy subjects from Japan; and 21 age-matched patients with primary open-angle glaucoma, 40 patients with normal pressure glaucoma, and a control group of 20 healthy subjects from the United States. MAIN OUTCOME MEASURES: Measurement of serum antibody titers and examination of optic disc and visual field parameters. METHODS: Serum immunoreactivity against heat shock proteins, including hsp27, alphaB-crystallin, and human and bacterial hsp60, was studied by enzyme-linked immunosorbent assay (ELISA). The relationship of serum antibody titers to glaucoma parameters, including mean deviation, neural rim area-to-disc area ratio, and peripapillary atrophy area-to-disc area ratio was examined. RESULTS: The serum ELISA titers of antibodies, including hsp27, alphaB-crystallin, human hsp60, and bacterial hsp60 antibodies, were higher in glaucoma patients compared with control subjects in both the Japanese and American groups (P: < 0.05). There was no association between the serum antibody titers and optic disc parameters in either group from Japan or the United States (P: > 0.05). CONCLUSIONS: These findings suggest that increased titers of circulating antibodies against heat shock proteins occur in both Japanese and American patients with glaucoma. The lack of a relationship between the level of serum antibody titers and the degree of glaucomatous damage in either ethnic group suggests that increased antibodies to heat shock proteins do not occur as an epiphenomenon of the glaucomatous neurodegeneration process.