The etiology of primary open angle glaucoma, a leading cause of age-related blindness, remains poorly defined, although elevated intraocular pressure (IOP) contributes to the disease progression. To better understand the mechanisms causing elevated IOP from aqueous humor circulation, we pursued proteomic analyses of trabecular meshwork (TM) from glaucoma and age-matched control donors. These analyses demonstrated that Cochlin, a protein associated with deafness disorder DFNA9, is present in glaucomatous but absent in normal TM. Cochlin was also detected in TM from the glaucomatous DBA/2J mouse preceding elevated IOP but found to be absent in three other mouse lines that do not develop elevated IOP. Histochemical analyses revealed co-deposits of Cochlin and mucopolysaccharide in human TM around Schlemm's canal, similar to that observed in the cochlea in DFNA9 deafness. Purified Cochlin was found to aggregate after sheer stress and to induce the aggregation of TM cells in vitro. Age-dependent in vivo increases in Cochlin were observed in glaucomatous TM, concomitant with a decrease in type II collagen, suggesting that Cochlin may disrupt the TM architecture and render components like collagen more susceptible to degradation and collapse. Overall, these observations suggest that Cochlin contributes to elevated IOP in primary open angle glaucoma through altered interactions within the TM extracellular matrix, resulting in cell aggregation, mucopolysaccharide deposition, and significant obstruction of the aqueous humor circulation.

Adult↗

PubMed2004

Appositional suprachoroidal hemorrhage: a case-control study.

PURPOSE: To identify the risk factors, prognostic factors, and clinical outcomes of patients with perioperative appositional suprachoroidal hemorrhage (ASCH). DESIGN: Case-control study. SETTING: Tertiary referral center. METHODS: Subjects included all patients with perioperative ASCH documented by B-scan ultrasound between May 1990 and March 2001. Two or three control patients were selected for each case, matched by surgeon, procedure, and date of surgery within 1 month. Surgery was performed as necessary. main outcome measures. The odds of ASCH associated with clinical risk factors. secondary outcome measure: visual acuity. RESULTS: Thirty-seven cases with ASCH were identified. Ninety-two procedure- and surgeon-matched control subjects (2.48:1) were selected. Twenty-six cases (71%) of ASCH were related to a glaucoma operation. Risk factors for the development of ASCH included previous vitrectomy (P = .003, odds ratio of 12) and older age (P = .007, odds ratio 1.57/decade of increasing age). Hypertension was found to be protective (P = .02, odds ratio of 0.33). Factors associated with a poor visual outcome in patients with ASCH included apposition >30 days (P = .01), history of uveitis (P = .04), history of dry age-related macular degeneration (P = .05), and history of extracapsular cataract extraction (P = .05). Median pre-ASCH visual acuity was 20/100, and final median visual acuity was 20/1600. CONCLUSIONS: Risk factors for the development of ASCH include previous vitrectomy and older age. Patients with these risk factors should be informed of their greater chance of poor visual acuity and anatomic outcomes secondary to the development of ASCH.

Adolescent↗

PubMed2003

Glutamate substitutions at a PKA consensus site are consistent with inactivation of calpain by phosphorylation.

Regulation of calpain by phosphorylation has often been suggested, but has proved difficult to detect. Calpains extracted from mammalian tissue are reported to contain 2-4 mol phosphate/mol of enzyme distributed over multiple sites, but phosphate groups are not detectable in the X-ray structures of recombinant calpain. Some serine and threonine residues in the large subunit of rat m-calpain were converted to aspartic or glutamic acid residues, at sites suggested by previous studies, to assess the probable effects of phosphate groups on the enzyme. Expression of the mutant calpains in Escherichia coli, and their heat stabilities, did not differ from those of the wild-type enzyme. m-Calpains with the mutations Ser50Asp, Ser50Glu, Ser67Glu, and Thr70Glu had the same specific activity and Ca(2+) requirement as the wild-type enzyme. In contrast, Ser369Asp-, Ser369Glu-, and Thr370Glu-m-calpain were inactive. This result is consistent with the recent report that phosphorylation at position 369 or 370 in vivo reduced m-calpain activation.

Amino Acid Substitution↗

PubMed2003

Surgical management of cataracts in children with juvenile rheumatoid arthritis-associated uveitis.

PURPOSE: To evaluate outcomes of cataract surgery with posterior chamber intraocular lens (IOL) implantation with or without trabeculectomy in children with juvenile rheumatoid arthritis (JRA)-associated uveitis. DESIGN: Interventional case series. METHOD: Retrospective chart review of five patients aged 12 years or younger with JRA-associated uveitis who underwent cataract surgery with posterior chamber IOL with or without trabeculectomy at the Cleveland Clinic Foundation from December 1995 to October 2001. RESULTS: Four female patients and one male patient ranging from age 7 to 12 years were identified. One patient had bilateral involvement; six eyes were included in the study. Three eyes underwent cataract extraction with posterior chamber IOL, and three underwent combined cataract surgery with posterior chamber IOL and trabeculectomy. Median age at surgery was 8.5 years, with a median follow-up of 43.5 months. Four of five children (five eyes) were on systemic methotrexate immunosuppressive therapy for a median length of 1.25 years before surgery. Two of five patients (three eyes) were also on additional systemic immunosuppressive or anti-inflammatory treatments. All eyes received frequent topical corticosteroid therapy for a median of 2 weeks preoperatively and 8.5 weeks postoperatively. A final postoperative Snellen visual acuity of 20/40 or better was achieved in all children. A median final visual acuity improvement of 7 Snellen lines was observed after cataract surgery. CONCLUSIONS: With adequate long-term preoperative and postoperative control of intraocular inflammation with systemic immunosuppressive therapy in addition to intensive topical corticosteroid treatment, children with JRA-associated uveitis can demonstrate favorable surgical outcomes after cataract surgery with posterior chamber IOL.

Administration, Topical↗

PubMed2003

Comparison of flap thickness reproducibility using microkeratomes with a second motor for advancement.

PURPOSE: To compare flap thickness and reproducibility of four different types of microkeratomes during LASIK. DESIGN: Retrospective, nonrandomized, comparative case series. PARTICIPANTS: Four hundred ninety consecutive eyes underwent LASIK and were evaluated by measuring the central flap thickness by subtractive pachymetry. METHODS: All flaps were created using the Bausch & Lomb (Miami, FL) Hansatome 180 head, the Alcon (Fort Worth, TX) Summit Krumeich Barraquer Microkeratome 160 head, the Moria (Antony, France) Carriazo Barraquer (CB) 130 head, or the Moria M2 110 head. RESULTS: The flap thickness measurements differed according to the microkeratome used and were 131+/-28 microm in 41 eyes (8.4%) with the Bausch & Lomb Hansatome 180 head, 162+/-21 microm in 127 eyes (25.9%) with the Alcon Summit Krumeich Barraquer Microkeratome (SKBM) 160 head, 157+/-40 microm in 65 eyes (13.3%) with the Moria CB 130 head, and 134+/-23 microm in 257 eyes (52.4%) with the Moria M2 110 head. The central flap thickness with the SKBM and Moria M2 was statistically significantly more reproducible than with the Moria CB (P< 0.0005). There is no correlation between flap thickness reproducibility and age, corneal thickness, or corneal keratometric values. However, considering all the microkeratomes, female gender had statistically significantly more variability than male gender (P<0.02). CONCLUSIONS: Based on these results, the greatest predictability of flap thickness was seen with the SKBM and Moria M2 microkeratomes, which both use a second motor for advancement. The greatest variability, noted with the Moria CB, was likely due to the manual translation feature and places further importance on the safety of the second motor and automation when performing LASIK.

Adult↗

PubMed2002

Chest computerized tomography in the evaluation of uveitis in elderly women.

PURPOSE: To describe the usefulness of chest computerized tomography (CT) in the evaluation of uveitis in elderly women and the clinical characteristics of patients with an abnormal chest CT scan. DESIGN: Prospective noncomparative case series. METHODS: We evaluated 30 elderly women, aged 61-83 years, with chronic iritis, vitritis, or choroiditis and with no definitive cause for their uveitis. All patients underwent a battery of diagnostic laboratory studies and chest CT. RESULTS: The diagnostic examination in most patients included serum angiotensin converting enzyme level, serum lysozyme, rapid plasma reagin level, fluorescent treponemal antibody-absorption test, purified protein derivative skin test, and chest x-rays. Chest CT performed on all patients showed parenchymal, mediastinal, and/or hilar adenopathy in 17 patients (57%). Histopathologic confirmation of sarcoidosis with noncaseating granulomas in the biopsy specimens was obtained in 14 patients: eight by mediastinoscopy, two by bronchoscopy, two by conjunctival biopsy, one by nasal biopsy, and one by vitreous biopsy. CONCLUSIONS: Chest CT can be useful in elderly female patients with chronic uveitis for identifying mediastinal lymphadenopathy and other lesions suggestive of sarcoidosis, as well as to help guide tissue confirmation and to rule out other diagnoses including lymphoma.

Aged↗

PubMed2002

Results of surgery for bilateral cataract associated with sensory nystagmus in children.

PURPOSE: To report the outcome of cataract surgery in children with bilateral cataract and preoperative sensory nystagmus. DESIGN: Interventional case series. METHODS: Retrospective review of 95 children who underwent surgery for bilateral cataract associated with sensory nystagmus. All patients lacked other structural ocular defects or neurologic abnormalities and were old enough at last follow-up to cooperate with recognition visual acuity testing. Outcome parameters studied were best-corrected postoperative visual acuity of the better eye and postoperative reduction or elimination of nystagmus. RESULTS: Mean age at surgery +/- SD was 2.0 +/- 2.6 years (range, 1 month to 13 years). Mean follow-up was 6.1 +/- 3.4 years (range, 2 months to 15 years). Best-corrected postoperative visual acuity of the better eye ranged from 20/25 to counting fingers and was 20/60 or better in 44 (46%), between 20/60 and 20/200 in 37 (39%), and 20/200 or worse in 14 (15%). Preoperative recognition visual acuity data were available for 16 of the older patients, and 5 or more lines of visual acuity improvement occurred in 5 (31%) including children as old as 9 years at the time of surgery. Nystagmus was reduced or eliminated postoperatively in 38 (40%). Mild, as opposed to severe, preoperative nystagmus was predictive of both a better visual acuity outcome (P =.004) and reduced or eliminated nystagmus postoperatively (P =.02). CONCLUSIONS: Good or even excellent visual acuity can be achieved after cataract surgery in some children with bilateral cataract and sensory nystagmus, and the nystagmus sometimes improves postoperatively.

Aphakia, Postcataract↗

PubMed2002

Immunity as a function of the unicellular state: implications of emerging genomic data.

Instead of being greeted as supporting the growing corpus of immunological theory, recent advances in the bioinformatic analysis of genomes have often surprised the discoverers and failed to attract the attention of immunologists. In fact, the view that multicellular immune systems are adaptations of already highly evolved unicellular immune systems that are capable of self/not-self discrimination can assist our comprehension of phenomena, such as 'junk' DNA, genetic polymorphism and the ubiquity of repetitive elements. For instance, the 'hidden transcriptome', revealed by run-on transcription of genes or repetitive elements, contains a diverse repertoire of RNA 'immune receptors' with the potential to form double-stranded RNA with viral RNA 'antigens', thus triggering intracellular alarms.

Alu Elements↗

PubMedDate not supplied

Using immobilized metal affinity chromatography, two-dimensional electrophoresis and mass spectrometry to identify hepatocellular proteins with copper-binding ability.

To further our knowledge of intracellular copper transport, we used a proteomics strategy to search for hepatic proteins with copper-binding ability. Hep G2 cytosolic and microsomal fractions were applied to a copper(II)-loaded immobilized metal-affinity chromatography (IMAC) column. Protein identification was performed with 2-D gel electrophoresis and mass spectrometry. We identified 48 cytosolic proteins and 19 microsomal proteins displaying copper-binding ability. These proteins are diverse in function. Fifty-two of the 67 proteins contain putative metal-binding domains. We have identified many components of the Hep G2 copper metalloproteome including a large number of proteins not previously known to bind copper.

Carrier Proteins↗