Augmentation of Lysosomal Phospholipase A2 Activity in the Anterior Chamber in Glaucoma.

AIM: The lysosomal enzyme in the anterior chamber has a crucial role in the digestion of the insoluble materials in the aqueous humor (AH). The dysfunction of AH filtration in the trabecular meshwork (TM) causes increasing AH outflow resistance in the TM. Those insoluble objects, including phospholipids, should be digested in the TM for normal outflow. The present study was conducted to explore the involvement of lysosomal phospholipase A2 (LPLA2), a phospholipid-degrading enzyme, of the AH in glaucoma using clinical AH specimens. MATERIALS AND METHODS: One hundred and twenty-five AH specimens were collected from patients. The measurement of LPLA2 activity in the AH was carried out using liposomes consisting of phosphatidylglycerol and N-acetylsphingosine (NAS). The correlation between the LPLA2 activity in the AH and ocular diseases was investigated. RESULTS: The human AH showed both transacylation of NAS and the release of fatty acids under acidic conditions but not at a neutral pH, which is consistent with the known properties of LPLA2. The LPLA2 activity in the AH was not affected by age or systemic disease. A comparison between ocular diseases showed that the AH specimens obtained from patients with glaucoma had significantly higher LPLA2 activity than the other ocular disease groups. DISCUSSION: The present findings suggest that the ascended level of LPLA2 activity in the AH of glaucoma patients is associated with the development of glaucoma.

Association of cryptogenic organizing pneumonia in bilateral anterior uveitis.

Two female patients with histories of cancer who showed cryptogenic organizing pneumonia (COP) complications and bilateral anterior uveitis with hypopyon were examined. Both patients had suffered from COP and received intermitted systemic corticosteroid administration (SCA). The first patient, a 65-year-old woman with a history of breast cancer, showed bilateral uveitis with hypopyon. The topical corticosteroid treatment was ineffective. After SCA for the treatment of COP was started, the hypopyon gradually dissipated. Upon termination of SCA, uveitis relapses were controlled by renewed SCA. The other patient, a 69-year-old woman with a history of ovarian cancer, showed bilateral anterior uveitis with hypopyon. Her intraocular outcome did not improve by the topical corticosteroid administration, but SCA that was applied to treat COP led to remission of uveitis. Imaging examinations, biochemical analysis, symptoms or HLA-B27 antigen screenings in either patient did not explain the development of uveitis. Bilateral anterior uveitis is commonly related to autoimmune disease or systemic syndrome. We report two cases with COP that developed bilateral anterior uveitis with hypopyon resistant to topical administration but responsive to systemic administration of corticosteroid. These findings suggest that COP can be associated with the etiology of anterior uveitis.

Effects of several anti-glaucoma medications on the circadian intraocular pressure fluctuations in patients with primary open-angle glaucoma.

PURPOSE: The purpose of the present study was to elucidate the effects of several anti-glaucoma medications on the circadian intraocular pressure (IOP) fluctuations in patients with primary open-angle glaucoma (POAG). PATIENTS AND METHODS: POAG patients (n=61; 61 eyes) with or without glaucoma medications were included. IOP measurement at 14 time points (12, 15, 18, 21, 0, 6, 9, 12, 15, 18, 21, 0, 6, and 9 o'clock) was performed over a period of 48 h. IOP changes occurring in the first 24 h and the subsequent 24 h were evaluated by several therapeutic factors. RESULTS: A nocturnal acrophase pattern was observed in all the eyes with POAG. The shape of the first 24 h IOP curve was similar to that of the following 24 h IOP curves. However, there were fewer overall IOP levels in the second 24 h time period. Circadian IOP fluctuation patterns exhibited in each eye on the 1st and 2nd days were single acrophase patterns: diurnal acrophase (1st day, 54.0%; 2nd day, 60.7%) and nocturnal acrophase (1st day, 36.1%; 2nd day, 31.1%), and no single acrophase patterns: flat (1st day, 6.6%; 2nd day, 4.9%) and double acrophase (1st day, 3.3%; 2nd day, 3.3%). Among the different medication groups, a nocturnal acrophase circadian pattern was observed in the patient groups being treated by combinations of prostaglandin analog (PG) and ß blocker or PG, ß blocker and carbonic anhydrase inhibitor (CAI). However, this was not apparent in patient groups with or without single anti-glaucoma medications or a combination of PG and CAI. CONCLUSIONS: The present study of IOP monitoring patients with POAG over a period of 48 h indicated that their changes in circadian patterns of IOP were affected by types of anti-glaucoma medications.

Lysosomal phospholipase A2 activity in pig aqueous humor.

PURPOSE: The present study was conducted to determine lysosomal phospholipase A2 (LPLA2) activity in the aqueous humor (AH) and to identify the possible sources of the LPLA2 found in the AH. METHODS: To detect LPLA2 activity in pig AH and ocular tissues, liposomes consisting of 1,2-dioleoylphosphatidylglycerol/N-acetylsphingosine were used as substrates in an activity assay under acidic conditions. The reaction products were separated by thin-layer chromatography. To identify the LPLA2 in pig AH, the AH was analyzed by Western immunoblot analysis with an anti-LPLA2 antibody. Distribution of the LPLA2 in pig ocular tissues was studied by determining its activity in individual tissue extracts. RESULTS: LPLA2 activity was detected in the AH obtained from pig eyes. Consistent with the known properties of LPLA2, the activity was heat-labile and undetectable at neutral pH. The immunoblot of pig AH showed the anti-LPLA2 antibody-reactive protein band. In addition, the specific activity of the enzyme, when normalized to volume, was higher in pig AH than in pig serum. Individual tissue extracts obtained from pig ocular tissues showed different specific activity of LPLA2. In particular, the extract prepared from the trabecular meshwork provided the highest specific activity. CONCLUSIONS: The present findings suggest that the phospholipase A2 activity found in pig AH under acidic conditions is due to LPLA2 and that it originates from ocular tissues surrounding the anterior chamber as well as plasma.

Tight junction proteins claudin-2 and -12 are critical for vitamin D-dependent Ca2+ absorption between enterocytes.

Ca(2+) is absorbed across intestinal epithelial monolayers via transcellular and paracellular pathways, and an active form of vitamin D(3), 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)], is known to promote intestinal Ca(2+) absorption. However, the molecules driving the paracellular Ca(2+) absorption and its vitamin D dependency remain obscure. Because the tight junction proteins claudins are suggested to form paracellular channels for selective ions between neighboring cells, we hypothesized that specific intestinal claudins might facilitate paracellular Ca(2+) transport and that expression of these claudins could be induced by 1alpha,25(OH)(2)D(3). Herein, we show, by using RNA interference and overexpression strategies, that claudin-2 and claudin-12 contribute to Ca(2+) absorption in intestinal epithelial cells. We also provide evidence showing that expression of claudins-2 and -12 is up-regulated in enterocytes in vitro and in vivo by 1alpha,25(OH)(2)D(3) through the vitamin D receptor. These findings strongly suggest that claudin-2- and/or claudin-12-based tight junctions form paracellular Ca(2+) channels in intestinal epithelia, and they highlight a novel mechanism behind vitamin D-dependent calcium homeostasis.

Experimental effect of retinoic acids on apoptosis during the development of diabetic retinopathy.

PURPOSE: This study was conducted to investigate whether retinoic acids (RAs) had any effect on apoptosis during the development of diabetic retinopathy. METHODS: To investigate whether RAs had any effect on apoptosis during the development of diabetic retinopathy, we housed 32 C57BL/6 male mice and induced diabetes in 24 by intra peritoneal injections of streptozotocin (STZ; Sigma, St Louis, MO) and treated 16 of the diabetic mice with the RAs, all-trans-retinoic acid (ATRA) (seven mice) and 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carboxamido] benzoic acid (Am580) (nine mice). The other eight mice were used as diabetic controls. We then measured apoptosis in the retina by TdT-dUTP terminal nick-end labeling assay. RESULTS: RAs inhibited the apoptosis of retinal cells in diabetic retinopathy. Many apoptotic cells were observed in retinas of the eight diabetic control mice (mean value and SD: 37.8 +/- 6.9), whereas when diabetic mice were treated with RAs, the number of apoptotic cells significantly decreased (mean value and SD: 9.9 +/- 6.4 for the seven ATRA-treated diabetic mice and 9.8 +/- 5.9 for the nine Am580-treated diabetic mice) (p < 0.05). CONCLUSION: Treatment with RAs decreases apoptosis during the development of diabetic retinopathy.

[Epidemic nosocomial keratoconjunctivitis caused by adenovirus type 4].

PURPOSE: To evaluate the clinical features of nosocomial epidemic keratoconjunctivitis(EKC) occurring in the ophthalmology ward of Sapporo Medical University Hospital and to devise preventive measures for it. MATERIALS AND METHODS: We studied the symptoms and clinical course of 2 patients who had EKC and 16 patients who had EKC caused by nosocomial infections in our hospital. We attempted to detect adenovirus antigen and viral DNA from conjunctival swabs and also to isolate the virus. RESULTS: The clinical symptoms of EKC were conjunctival hyperemia in 18 patients(100%), conjunctival follicles in 11 patients (61.1%), discharge in 8 patients(44.4%), superficial punctate keratopathy in 7 patients(38.9%), swelling of the eyelids in 3 patients(16.7%), and fever in 3 patients(16.7%). 72% were positive for Adeno-check. Adenovirus type 4 was isolated from the conjunctival swabs. We considered that the route of hospital infection was infection from the doctor's hands, from eye drops, and from contact lenses. We disclosed that nosocomical EKC had occurred in our hospital. The hospital infection was eliminated by closing the ophthalmology ward and sterilizing instruments and washing hands. CONCLUSIONS: The delay of proper measures increased the risk of nosocomical infection. We recognized the importance of careful observation of patients and immediate preventive efforts in nosocomical infection.