Biomedical subjects

Hidenobu Tanihara

Publications and source records attributed to Hidenobu Tanihara.

At least 19 recordsLinked to original sources

PubMed2006

Loss of vision due to a physiologic pituitary enlargement during normal pregnancy.

BACKGROUND: Physiologic pituitary enlargement during normal pregnancy is well known, but we are unaware of previous reports on a natural course of visual loss due to this disease. METHODS: A 30-year-old woman presented blurred vision in the left eye from the 30th week of pregnancy. At 38 weeks visual acuity was 0.9 in the left eye. Automated perimetry revealed a mild central visual defect in the left eye. A magnetic resonance imaging (MRI) scan revealed pituitary enlargement with compression of the anterior optic chiasm. We observed the natural course of this case. RESULTS: At 16 weeks after delivery, visual acuity was 1.5 in both eyes with normal visual field, and an MRI scan revealed a normal-sized pituitary without compression of the optic chiasm. CONCLUSIONS: Ophthalmologists should be aware of visual loss by physiologic pituitary enlargement to avoid unreasonable neurosurgical procedures.

Adult↗

PubMed2006

Induction of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs correlates with outcome of acute experimental pseudomonal keratitis.

This study aimed to investigate expressions and sources of matrix metalloproteinases (MMP)-2 and MMP-9, and of tissue inhibitors of MMP (TIMP)-1 and TIMP-2 in experimental Pseudomonas aeruginosa keratitis in rabbits. Pseudomonal keratitis was induced in New Zealand white rabbits, and macroscopic and microscopic examinations were performed at appropriate time points (3, 9, 12, 18, 24, 72 h). Expressions and sources of MMP-2, 9, and TIMP-1, 2 were determined using immunohistochemistry, gelatin zymography, ELISA, and RT-PCR. A typical corneal ulcer with a ring abscess was observed 12-72 h post-infection (p.i.) with P. aeruginosa. In microscopic examinations, massive inflammatory cell (mostly polymorphonuclear leukocytes, PMNs) infiltration and liquefactive necrosis were characteristic features. MMP-2 was constitutively expressed in keratocytes, and its expression was not apparently enhanced after pseudomonal infection as evidenced by zymography, immunostaining, and RT-PCR. However, MMP-9 and its activated form were induced, and were significantly enhanced 12-24 h p.i. MMP-9 appeared to derive from PMNs rather than from resident corneal cells. TIMP-1 was expressed in PMNs, macrophages, and keratocytes, and its expression was enhanced 72 h p.i. Although TIMP-2 was constitutively expressed as seen by immunostaining and RT-PCR, its concentration was below detection limits during the experiments. We demonstrated that MMP-9 was one of the important factors for corneal tissue destruction, because it was induced and significantly expressed in keratocytes and inflammatory cells after pseudomonal infection. Although TIMP-1 was expressed in later stages of infection, enhancement and activation of MMP-9 were much faster and stronger than those of TIMP-1, thereby facilitating tissue destruction leading to corneal ulceration.

Acute Disease↗

PubMed2006

Elevated neprilysin activity in vitreous of patients with proliferative diabetic retinopathy.

PURPOSE: Diabetic retinopathy (DR) is the leading cause of blindness in the industrialized world. Hyperglycemia induces retinal hypoxia, which upregulates a range of vasoactive factors that may lead to macular edema and/or angiogenesis, and hence potentially to sight-threatening retinopathy. The control of signal-peptide activity by cell-surface proteases is one of the main factors regulating the development and behavior of organisms. In mammals, neprilysin is known to play a key role in these processes, and its inactivation can initiate cellular disorganization. Neprilysin is a rate-limiting peptidase involved in the physiological degradation of amyloid beta (Abeta) in the brain. In this study, we measured both the enzymatic activity of neprilysin and the concentration of Abeta in patients with proliferative DR (as compared to their levels in patients with macular hole), and we analyzed their association. METHODS: In vitreous samples collected from patients who underwent vitrectomy, an HPLC-fluorometric system (recently established by us), and sensitive and specific enzyme-linked immunosorbent assays were used to determine the enzymatic activity of neprilysin and the concentration of Abeta. RESULTS: By comparison with the levels in the control (macular-hole) patients, there was a significant increase in neprilysin activity level and a significant decrease in Abeta level in proliferative DR patients. There was a significant inverse correlation between neprilysin and Abeta among all subjects. CONCLUSIONS: Neprilysin activity and Abeta concentrations displayed converse changes in patients with proliferative DR.

Amyloid beta-Peptides↗

PubMed2006

Choroidal dye filling velocity in patients with Vogt-Koyanagi-Harada disease.

PURPOSE: To evaluate quantitative choroidal dye filling velocity in patients with Vogt-Koyanagi-Harada disease (VKH) before and after corticosteroid treatment using indocyanine green (ICG) angiography. METHODS: ICG angiography was performed in seven VKH patients before and after systemic corticosteroid treatment. Choroidal dye curves were obtained by image analysis software and analyzed using an exponential model. The model's time constant (tau) was used to evaluate choroidal dye filling velocity. RESULTS: Compared with controls, acute phase choroidal tau values in VKH patients were significantly longer, suggesting choroidal circulation disturbance. During the recovery phase, choroidal tau values were significantly shortened, suggesting choroidal circulatory disturbance improvement. CONCLUSION: Choroidal dye filling velocity may be useful for VKH diagnosis and verification of corticosteroid treatment effectiveness.

Adult↗

PubMed2006

Thioredoxin inhibits NMDA-induced neurotoxicity in the rat retina.

Thioredoxin (TRX) plays a variety of redox-related roles in organisms. To investigate its function as an endogenous redox regulator in NMDA-induced retinal neurotoxicity, we injected NMDA with TRX, mutant TRX or saline into the vitreous cavity of rat eyes. Retinal ganglion cells were rescued by TRX, compared with saline, when evaluated by retrograde labeling analysis at 7 days after NMDA injection. TRX, but not its mutant form, prevented NMDA-induced apoptosis in the retina, as measured by terminal deoxynucleotidyl transferase-mediated UTP nick-end labeling. The induction of caspase 3 and 9, but not caspase 8, by NMDA was significantly lower in TRX-treated eyes than in saline-treated eyes. NMDA-induced activation of the MAPKs, p38 kinase and c-Jun N-terminal kinase after 6 h and of the MAPK kinases (MKKs) MKK3/6 and MKK4 after 3 h was markedly suppressed in retinal ganglion cells by TRX but not by the mutant form. NMDA-induced increases in protein carbonylation, nitrosylation and lipid peroxidation were also suppressed in TRX-treated eyes. We concluded that the intravitreous injection of TRX effectively attenuated NMDA-induced retinal cell damage and that suppression of oxidative stress and inhibition of apoptotic signaling pathways were involved in this neuroprotection.

Animals↗

PubMed2006

Posterior vitreous detachment induced by nattokinase (subtilisin NAT): a novel enzyme for pharmacologic vitreolysis.

PURPOSE: To investigate the effects of intravitreal injection of nattokinase (subtilisin NAT), a serine protease that is produced by Bacillus subtilis (natto), for induction of posterior vitreous detachment (PVD). METHODS: Different doses of nattokinase (1, 0.1, or 0.01 fibrin-degradation units [FU]) or physiologic saline as a control were injected into the vitreous cavity of rabbit eyes. Scanning electron microscopy was used to observe the retinal surfaces of four rabbit eyes per concentration. Histologic alterations were assessed by light microscopy, using four eyes from each group. Electroretinography (ERG) was performed to observe retinal function, ranging from 1 hour to 1 week after the nattokinase (1 or 0.1 FU) or saline solution administration, using four eyes from each group at each time point. Also, findings in all rabbits were monitored by slit lamp examination and by indirect ophthalmoscopy with a 20-D lens. RESULTS: Scanning electron microscopy showed smooth retinal surfaces, indicating the occurrence of PVD at 30 minutes after intervention in all the experimental eyes injected with 0.1 or 1.0 FU nattokinase, but none of the control eyes. Light microscopy and ERG analysis showed no critical change even after the use of 0.1 FU nattokinase, an amount sufficient to induce PVD. However, toxicity in the forms of preretinal hemorrhage and ERG changes was noted with the higher dose (1 FU) of nattokinase. CONCLUSIONS: The results suggested that nattokinase is a useful enzyme for pharmacologic vitreolysis because of its efficacy in inducing PVD.

Animals↗

PubMed2005

NMDA-induced retinal injury is mediated by an endoplasmic reticulum stress-related protein, CHOP/GADD153.

We investigated the role of an endoplasmic reticulum stress-associated protein, CHOP/GADD153, after NMDA-induced mouse retinal damage. After injection of NMDA into the vitreous, TUNEL-positive cells were detected in the retinal ganglion cell layer (GCL) and inner nuclear layer (INL) at 6 h after NMDA injection, and these gradually increased in number up to 24 h. Analysis by real-time RT-PCR revealed that CHOP mRNA was induced by about 3-fold, at 2 h after NMDA injection. Immunoreactivity for the CHOP protein was intense in cells of the GCL following NMDA treatment. Immunoblot analysis showed that NMDA injection increased the expression of CHOP protein in the retina. Compared with wild-type mice, CHOP/ mice were more resistant to NMDA-induced retinal cell death as determined by TUNEL assay. At 7 days after NMDA treatment, the thickness of the inner plexiform layer and INL were larger in CHOP/ mice than in wild-type mice. The number of residual cells in the GCL following NMDA treatment was significantly higher in CHOP/ mice than in wild-type mice. In conclusion, CHOP is induced in mouse retina by NMDA treatment, and CHOP/ mice are more resistant to NMDA-induced retinal damage, suggesting that CHOP plays an important role in NMDA-induced retinal cell death.

Animals↗

PubMed2005

Activation of canonical Wnt pathway promotes proliferation of retinal stem cells derived from adult mouse ciliary margin.

Adult retinal stem cells represent a possible cell source for the treatment of retinal degeneration. However, only a small number of stem cells reside in the ciliary margin. The present study aimed to promote the proliferation of adult retinal stem cells via the Wnt signaling pathway. Ciliary margin cells from 8-week-old mice were dissociated and cultured to allow sphere colony formation. Wnt3a, a glycogen synthase kinase (GSK) 3 inhibitor, fibroblast growth factor (FGF) 2, and a FGF receptor inhibitor were then applied in the culture media. The primary spheres were dissociated to prepare either monolayer or secondary sphere cultures. Wnt3a increased the size of the primary spheres and the number of Ki-67-positive proliferating cells in monolayer culture. The Wnt3a-treated primary sphere cells were capable of self-renewal and gave rise to fourfold the number of secondary spheres compared with nontreated sphere cells. These cells also retained their multilineage potential to express several retinal markers under differentiating culture conditions. The Wnt3a-treated cells showed nuclear accumulation of beta-catenin, and a GSK3 inhibitor, SB216763, mimicked the mitogenic activity of Wnt3a. The proliferative effect of SB216763 was attenuated by an FGF receptor inhibitor but was enhanced by FGF2, with Ki-67-positive cells reaching over 70% of the total cells. Wnt3a and SB216763 promoted the proliferation of retinal stem cells, and this was partly dependent on FGF2 signaling. A combination of Wnt and FGF signaling may provide a therapeutic strategy for in vitro expansion or in vivo activation of adult retinal stem cells.

Animals↗

PubMed2005

Ocular amyloid angiopathy associated with familial amyloidotic polyneuropathy caused by amyloidogenic transthyretin Y114C.

PURPOSE: To report the clinicopathological findings for a unique ocular amyloid angiopathy in patients with familial amyloidotic polyneuropathy (FAP) caused by amyloidogenic transthyretin Y114C. DESIGN: Three case reports. METHODS: Retrospective review of clinicopathological findings, course, and treatment of the 3 patients. MAIN OUTCOME MEASURES: Visual acuity, intraocular pressure, fundus photography, fluorescein angiography (FA), indocyanine green angiography, and histopathological analysis. RESULTS: In the 32-year-old patient, in the early stage of FAP, indocyanine green angiography demonstrated multiple sites of hyperfluorescence, with staining along major choroidal veins. Retinal vessels appeared normal clinically and on FA. In the 48-year-old patient, who had late-stage FAP, examination of the fundus revealed pinpoint white amyloid opacities over the retinal surface, sheathing of retinal vessels, and scattered retinal hemorrhages. Fluorescein angiography showed vascular closure, focal staining, and microaneurysms. Indocyanine green angiography revealed multiple sites of hyperfluorescence, with staining along retinal and choroidal vessels. Examination during follow-up revealed that these vascular changes continued to progress. Histopathological study of an eye obtained at autopsy from the 49-year-old patient revealed marked intravascular and extravascular amyloid deposition. CONCLUSIONS: Severe and progressive amyloid angiopathy causing visual disturbance was seen in patients with FAP caused by amyloidogenic transthyretin Y114C.

Adult↗

PubMed2005

Autoimmunity against neurofilament protein and its possible association with HLA-DRB1*1502 allele in glaucoma.

Glaucoma is understood as a neurodegenerative disease and intraocular pressure has been regarded as the major risk factors for the optic nerve damages. However, recent studies suggested that several risk factors including autoimmunity are also shown to play important roles in glaucoma. To identify the retinal antigen in glaucoma, we used the serological analysis of recombinant cDNA expression libraries (SEREX) approach and quantified IgG antibodies directed against the identified antigens in an ELISA. We identified neurofilament protein and the prevalence of anti-bovine neurofilament light subunit (NF-L) autoantibodies in glaucomatous patients was significantly higher than in healthy controls and patients with other uveitic and optic nerve diseases (P<0.05). In addition, our immunogenetic analysis showed a possible association between HLA-DRB1*1502 allele and the patients positive for anti-NF-L autoantibodies. It suggests that the HLA class II-linked gene may be involved in development of autoimmunity in patients with glaucoma.

Adult↗

PubMed2005

Preferential differentiation of neural progenitor cells into the glial lineage through gp130 signaling in N-methyl-D-aspartate-treated retinas.

The purpose of this study was to investigate the differentiation of neural progenitor cells (NPCs) following retinal transplantation in N-methyl-D-aspartate (NMDA)-treated eyes. NMDA was injected into the vitreous cavity of adult rat eyes. NPCs were prepared from telencephalic neuroepithelium of enhanced green fluorescence protein (EGFP) transgenic mice on embryonic day 14.5. A cell suspension was injected into the vitreous cavity in experimental eyes. Immunohistochemistry was conducted at 1, 2 or 4 weeks after transplantation of NPCs in an effort to determine the survival and differentiation of transplanted NPCs. Similar experiments were conducted using glycoprotein (gp)130-null (-/-) mice. Examination of retinal sections revealed that transplanted NPCs could survive for at least 4 weeks in NMDA-treated retinas. Immunohistochemical studies for specific cell-type markers revealed that, among the transplanted NPCs at 2 weeks after transplantation, the mean percentage (+/-standard deviation) of glial fibrillary acidic protein (GFAP)-positive (glial) cells was 63.5 +/- 7.4%, demonstrating the differentiation of transplanted NPCs with a preference for the glial lineage. Furthermore, the mean percentage of betaIII-tubulin-positive (mature neuronal) cells was 18.8 +/- 4.5%. Following transplantation of NPCs isolated from gp130-/- mice into NMDA-treated retinas, the mean percentage of GFAP-positive cells (17.6 +/- 7.0%), was significantly lower than that in NPCs isolated from wild-type mice (59.1 +/- 6.0%, P = 0.04, Mann-Whitney U test). Preferential differentiation of NPCs into the glial lineage is induced through gp130 signaling in NMDA-treated eyes.

Animals↗

PubMed2005

Intravitreal plasmin injection activates endogenous matrix metalloproteinase-2 in rabbit and human vitreous.

PURPOSE: To investigate the effect of exogenous plasmin administration on the activity of endogenous matrix metalloproteinase-2 (MMP-2) in rabbit and human vitreous. DESIGN: Experimental animal study and interventional case series. METHODS: Human plasmin was injected into rabbit eyes. The active/pro-MMP-2 ratio in vitreous samples was calculated using the gelatin zymography. Scanning electron microscopy (SEM) was performed to observe the retinal surface. To evaluate the time course of MMP-2 activity, vitreous samples were collected after the injection of 0.5 IU of plasmin, and the active/pro-MMP-2 ratio was calculated in the same manner. Immunohistochemical analysis was performed to confirm the presence of MT1-MMP in the rabbit eye. Human vitreous samples obtained from vitreous surgeries were also used for similar studies. RESULTS: The active/pro-MMP-2 ratios in the vitreous after the injection of 0.25 IU or 0.5 IU of plasmin were significantly higher than that of the control (P < .05). SEM demonstrated that plasmin-treated eyes showed a smooth retinal surface that was dose-dependent. Time course evaluation of the active/pro-MMP-2 ratio in the vitreous after the administration of 0.5 IU of plasmin found a significant difference between the 5 and 15 minutes data points compared with that seen for the control. Immunohistochemical study revealed the presence of MT1-MMP in the inner retina. In human samples, the active/pro-MMP-2 ratio after the plasmin injection was significantly higher than the ratio observed before injection. CONCLUSIONS: Our results suggested that activation of endogenous MMP-2 by exogenous plasmin is associated with the induction of posterior vitreous detachment.

Aged↗

PubMed2005

Rho-associated protein kinase inhibitor, Y-27632, induces alterations in adhesion, contraction and motility in cultured human trabecular meshwork cells.

We investigated the roles of Rho-associated protein kinase (ROCK) in regulating activities such as adhesion, contraction and migration in cultured human trabecular meshwork (TM) cells. Human TM cells in culture were treated with Y-27632, a specific ROCK inhibitor. Trypan blue exclusion test and TUNEL staining showed little or no direct toxicity of Y-27632 on TM cells. By MTT assay, Y-27632 did not significantly affect the proliferation of TM cells. The cell adhesion assay showed that Y-27632 promoted the cell adhesiveness to both fibronectin and collagen type I in a dose-dependent manner. Collagen gel contraction activity of TM cells was significantly inhibited by the treatment of Y-27632 in a dose-dependent manner. The addition of Y-27632 accelerated motility of TM cells in wound healing assay. Phosphorylated LIM kinase 2 and cofilin, related to actin bundling and integrin clustering, were dephosphorylated (activated) by Y-27632. In conclusion, Y-27632 elicits profound effects on TM cell activities including adhesion, gel contraction, and cell motility. These Y-27632-induced changes of TM cells may be relevance to the physiology of the aqueous outflow system.

Amides↗

PubMed2005

Trans-Tenon's retrobulbar triamcinolone acetonide infusion for refractory diabetic macular edema after vitrectomy.

PURPOSE: To evaluate the efficacy and safety of trans-Tenon's retrobulbar triamcinolone acetonide (TA) infusion for the treatment of refractory diabetic macular edema (DME) after vitrectomy. METHODS: After topical anesthesia, 20 eyes from 20 patients with persistent DME after pars plana vitrectomy were treated with trans-Tenon's retrobulbar infusion of 40 mg TA through an inferotemporal approach. The mean duration (+/-SD) between vitrectomy and trans-Tenon's retrobulbar TA infusion was 11.4+/-7.9 months. The mean follow-up period (+/-SD) after trans-Tenon's retrobulbar TA infusion was 13.3+/-2.8 months. RESULTS: At 1 week after trans-Tenon's retrobulbar TA infusion, the mean central retinal thickness (+/-SD) measured by optical coherence tomography was 381+/-99 mum, which was a statistically significant decrease in comparison with the preoperative thickness (555+/-112 mum) (P<0.001). Additional trans-Tenon's retrobulbar TA infusions were performed in ten eyes (50%), due to the recurrence of DME at 6.6+/-3.0 months after the first TA infusion. At the final examination, macular edema resolved in 13 (65%), improved in four (20%), and remained unchanged in three (15%) of the 20 eyes. At 1 month after trans-Tenon's retrobulbar TA infusion, the mean laser flare value (+/-SD) was 9.6+/-3.0 photon/ms, which was a statistically significant decrease in comparison with the preoperative value (15.5+/-5.9 photon/ms) (P<0.01). Furthermore, in ten eyes (50%) with recurrent DME, re-elevated laser flare values were observed prior to the recurrence of DME. The final best-corrected Snellen visual acuity improved by two or more lines in nine eyes (45%), and remained unchanged in 11 eyes (55.0%). IOP elevation equal to or higher than 21 mmHg was observed in three (15%) of the 20 eyes with TA infusion, and was controlled by topical medications. No other injection-related complications were observed. CONCLUSION: Trans-Tenon's retrobulbar TA infusion is an effective and safe method for the treatment of refractory DME, which is present even after vitrectomy.

Adult↗

PubMed2005

Association between glaucoma and gene polymorphism of endothelin type A receptor.

PURPOSE: Endothelin 1 (ET-1), a potent vasoconstrictor, may affect regulation of intraocular pressure and ocular vessel tone. Thus, ET-1 and its receptors may contribute to development of glaucoma. We investigated whether gene polymorphisms of ET-1 (EDN1) and its receptors ETA (EDNRA) and ETB (EDNRB) were associated with glaucoma phenotypes and clinical features. METHODS: We studied 224 normal Japanese controls and 426 open angle glaucoma (OAG) patients including 176 with primary open angle glaucoma (POAG) and 250 with normal tension glaucoma (NTG). Nine single nucleotide polymorphisms were detected among the participants using the Invader assay; four for EDN1 (T-1370G, +138/ex1 del/ins, G8002A, K198N), four for EDNRA (G-231A, H323H, C+70G, C+1222T), and one for EDNRB (L277L). Genotype distributions were compared between normal controls and OAG. Age at diagnosis, untreated maximum intraocular pressure (IOP), and visual field defects at diagnosis were examined for association with polymorphisms. RESULTS: Of the 9 polymorphisms, genotype distributions showed no significant differences between OAG patients and controls adjusted by age. The GG genotype of EDNRA/C+70G was associated with worse visual field defects in NTG patients (p=0.014; Mann-Whitney U test, and p=0.027; logistic regression analysis). CONCLUSIONS: The polymorphism of EDNRA/C+70G may be related to NTG risk factors.

Aged↗

PubMed2005

Trans-tenon retrobulbar triamcinolone injection for macular edema associated with branch retinal vein occlusion remaining after vitrectomy.

PURPOSE: To evaluate the effectiveness and safety of trans-Tenon retrobulbar triamcinolone injection for macular edema associated with branch retinal vein occlusion (BRVO) after vitrectomy. DESIGN: Prospective interventional case series. METHODS: The study included 20 eyes of 20 patients with BRVO, characterized by macular edema lasting more than 3 months after vitrectomy. Trans-Tenon retrobulbar injection of 40 mg triamcinolone was performed, and visual and anatomic responses were evaluated. RESULTS: Mean foveal thickness was 499.4 +/- 209.1 microm preoperatively, 281.8 +/- 110.1 microm at 2-week follow-up, and 196.9 +/- 92.1 microm at 6-month follow-up (P < .0001, at 2 weeks and 6 months, paired t test). Improvement of visual acuity by at least 0.2 logMAR (logarithm of the minimum angle of resolution) was seen in 14 (70%) of the 20 eyes. CONCLUSIONS: Trans-Tenon retrobulbar injection of triamcinolone may be an alternative for additional treatment of eyes with BRVO that remains after vitrectomy.

Aged↗

PubMed2005

The effect of subtenon triamcinolone acetonide injection for diabetic macular edema on retinal and choroidal circulation.

PURPOSE: To evaluate changes in retinal and choroidal circulation after subtenon triamcinolone acetonide (TA) injection for diabetic macular edema. DESIGN: Prospective interventional case series. METHODS: Thirteen eyes of 13 patients with diabetic macular edema were studied. Fluorescein and indocyanine green angiograms were performed at three periods: before the injection and 1 week and 6 months after subtenon injection of TA (40 mg). Retinal arteriovenous passage time (as an indicator of retinal circulation) and choroidal tau (as an indicator of early filling velocity of choroid) were obtained with image analysis software. RESULTS: Choroidal tau values before and 1 week after subtenon TA injection were, respectively, 3.2 +/- 0.4 and 4.0 +/- 0.7 seconds, which showed a significant delay (P = .01, Wilcoxon signed-rank test). The delayed choroidal tau values returned to pretreatment level at 6 months after TA injection. In contrast, the arteriovenous passage time remained unchanged. CONCLUSION: Subtenon TA injection transiently influences choroidal blood flow.

Blood Circulation↗

PubMed2005

Transthyretin synthesis in rabbit ciliary pigment epithelium.

Ocular symptoms of transthyretin (TTR)-related familial amyloidotic polyneuropathy (FAP) suggest that ciliary pigment epithelium (CPE) may synthesize TTR and its TTR may lead to amyloid formation in addition to TTR from vessels and retinal pigment epithelium (RPE). To clarify sites of TTR synthesis in ocular tissues, we performed in situ hybridization and reverse transcription-polymerase chain reaction (RT-PCR) for qualitative detection of TTR mRNA. In addition, we quantified levels of TTR mRNA expression by means of real-time quantitative RT-PCR. Furthermore, although TTR is an anti-acute phase protein in serum level, no reports on changes in TTR expression in ocular tissues during acute inflammation exist. To investigate changes in TTR expression in ocular tissues during inflammation, we induced uveitis by endotoxin challenge in rabbits and used real-time quantitative RT-PCR to examine changes in TTR mRNA expression in ocular tissues. In situ hybridization and RT-PCR qualitatively demonstrated TTR mRNA not only in RPE but also in CPE. Real-time quantitative RT-PCR showed that the level of TTR mRNA expression in the CPE was about one-third of that in the RPE. TTR mRNA expression in ocular tissues decreased as the degree of inflammation increased. These results suggest that TTR synthesized in the CPE may lead to ocular manifestations, especially glaucoma, in FAP. TTR mRNA also acts as an anti-acute phase reactant in ocular tissues.

Animals↗