Oklahoma City, OK, United States
Oklahoma City, OK, United States

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Dao J.B.,Duke Eye Center | Sarkisian S.R.,McGee Eye Institute | Freedman S.F.,Duke Eye Center
Journal of Glaucoma | Year: 2014

BACKGROUND:: Aphakic and juvenile open-angle glaucoma (JOAG) cases often prove to be challenging to manage, frequently requiring surgical intervention. Angle surgery has some reported success in these cases. PURPOSE:: The purpose of this study was to evaluate 360-degree trabeculotomy, facilitated by iTrack, for refractory aphakic glaucoma and JOAG. PATIENTS AND METHODS:: This study was conducted to evaluate the success and complication rates of illuminated microcatheter-assisted 360-degree trabeculotomy for aphakic glaucoma and JOAG (2 surgeons/2 sites, 2008 to 2011). The success of this surgery was defined as intraocular pressure ≤22 mm Hg with >30% reduction, without disease progression, oral glaucoma medications, or additional glaucoma surgery. One eye per subject was analyzed. All had gonioscopically open angles preoperatively. RESULTS:: A total of 23 eyes status post iTrack-facilitated 360-degree trabeculotomy, 13 aphakic glaucoma cases (mean age 3.1 y at surgery), and 10 JOAG cases (mean age, 18.6 y) were included in the study. Complete cannulation/opening of the Schlemm canal occurred intraoperatively in 8 aphakic and in all JOAG cases. Success rates achieved at last follow-up were as follows: 8/13 (62%) aphakic glaucoma cases and 9/10 (90%) JOAG cases. Preoperative versus final intraocular pressure decreased for all surgically successful eyes (35.5±3.9 vs. 17.3±4.6 mm Hg for aphakic glaucoma, P<0.0001, after mean 30 mo and 30.7±7.4 vs. 13.4±2.8 mm Hg for JOAG, P=0.0001, after mean 10 mo). All trabeculotomy failures (n=5) occurred within 5 months. Complications included vitreous hemorrhage (2 aphakic eyes) and transient choroidal effusion (1 aphakic eye). CONCLUSIONS:: iTrack-facilitated 360-degree trabeculotomy shows early promise for initial surgical treatment of medically refractory aphakic glaucoma and JOAG, with few complications and without affecting future surgical options. Copyright © 2013 by Lippincott Williams & Wilkins.


Ikuta T.,University of Georgia | Thatte H.S.,Harvard University | Tang J.X.,Brown University | Mukerji I.,Wesleyan University | And 8 more authors.
Archives of Biochemistry and Biophysics | Year: 2011

We previously demonstrated that inhaling nitric oxide (NO) increases the oxygen affinity of sickle red blood cells (RBCs) in patients with sickle cell disease (SCD). Our recent studies found that NO lowered the P50 values of sickle hemoglobin (HbS) hemolysates but did not increase methemoglobin (metHb) levels, supporting the role of NO, but not metHb, in the oxygen affinity of HbS. Here we examine the mechanism by which NO increases HbS oxygen affinity. Because anti-sickling agents increase sickle RBC oxygen affinity, we first determined whether NO exhibits anti-sickling properties. The viscosity of HbS hemolysates, measured by falling ball assays, increased upon deoxygenation; NO treatment reduced the increment. Multiphoton microscopic analyses showed smaller HbS polymers in deoxygenated sickle RBCs and HbS hemolysates exposed to NO. These results suggest that NO inhibits HbS polymer formation and has anti-sickling properties. Furthermore, we found that HbS treated with NO exhibits an isoelectric point similar to that of HbA, suggesting that NO alters the electric charge of HbS. NO-HbS adducts had the same elution time as HbA upon high performance liquid chromatography analysis. This study demonstrates that NO may disrupt HbS polymers by abolishing the excess positive charge of HbS, resulting in increased oxygen affinity. © 2011 Elsevier Inc. All rights reserved.


Brown C.R.,University of Iowa | Wagoner M.D.,University of Iowa | Welder J.D.,University of Iowa | Cohen A.W.,McGee Eye Institute | And 3 more authors.
Cornea | Year: 2014

PURPOSE:: The aim of this study was to evaluate and compare the outcomes of Boston keratoprosthesis type 1 (Kpro-1) in eyes with herpes simplex virus (HSV) and herpes zoster virus (HZV) keratopathy. METHODS:: A retrospective review was performed of the medical records of every patient treated with a Boston Kpro-1 at the University of Iowa Hospitals and Clinics between January 1, 2008 and July 1, 2012. Eyes with visual loss due to HSV or HZV keratopathy were included in the statistical analysis. The main outcome measures were graft retention, postoperative complications, and visual outcome. RESULTS:: Nine eyes met the inclusion criteria, including 5 eyes in the HSV group and 4 eyes in the HZV group. The graft retention rate was 100% in the HSV group after a mean follow-up of 48.4 months, compared with 25% in the HZV group after 50.5 months (P = 0.048). There were 3 cases of microbial keratitis, including 2 eyes that also developed endophthalmitis, in the HZV group, compared with no cases in the HSV group (P = 0.048). There was significantly better best-corrected visual acuity at the most recent examination in the HSV group than in the HZV group (P = 0.019). All 5 HSV eyes had improved best-corrected visual acuity compared with preoperative acuity, whereas only 1 HZV eye experienced a similar result (P = 0.048). CONCLUSIONS:: Kpro-1 is associated with an excellent prognosis for graft retention, acceptably low prevalence of sight-threatening complications, and highly satisfactory visual improvement in eyes with HSV keratopathy, but not in eyes with HZV keratopathy. Copyright © 2014 by Lippincott Williams & Wilkins.


Gupta V.K.,The University of Oklahoma Health Sciences Center | Gupta V.K.,McGee Eye Institute | Rajala A.,The University of Oklahoma Health Sciences Center | Rajala A.,McGee Eye Institute | And 2 more authors.
Cell Communication and Signaling | Year: 2015

Background: Phosphatidylinositol 3-Kinases (PI3Ks) are a family of lipid kinases that phosphorylate the D3-hydroxyls of the inositol ring of phosphoinositides, and are responsible for coordinating a diverse range of cellular functions. A canonical pathway of activation of PI3Ks through the interaction of RA-domain with Ras proteins has been well established. In retinal photoreceptors, we have identified a non-canonical pathway of PI3Kγ activation through the interaction of its RA-domain with a putative Ras-like domain (RLD) in alpha subunit of cyclic nucleotide-gated channel (CNGA1) in retinal rod photoreceptors. Results: The interaction between PI3Kγ and CNGA1 does not appear to play a role in regulation of CNG channel activity, but PI3Kγ uses CNGA1 as an anchoring module to achieve close proximity to its substrate to generate D3-phosphoinositides. Conclusions: Our studies suggest a functional non-canonical PI3Kγ activation in retinal rod photoreceptor cells. © 2015 Gupta et al.; licensee BioMed Central.


Adesina O.-O.O.,University of Oklahoma | Vickery J.A.,McGee Eye Institute | Ferguson C.L.,McGee Eye Institute | Stone D.U.,University of Oklahoma | Stone D.U.,McGee Eye Institute
Eye and Contact Lens | Year: 2013

Objectives: The aim was to discuss the use of a conjunctival flap for treatment of keratolysis of a keratoprosthesis (Kpro) donor graft in a patient fitted with a cosmetic contact lens. Methods: Keratolysis developed in the donor graft of a Boston Kpro; this was associated with the use of a cosmetic contact lens. A conjunctival flap was used to stabilize the graft. The literature is reviewed for similar cases, and the rationale for the intervention is described and discussed. Results: Reinforcement of the graft with a conjunctival flap resulted in an arrest in stromal melting and stabilization of visual acuity. Conclusions: Low Dk opaque contact lenses may be a risk factor for keratolysis after Kpro. A conjunctival flap technique can provide stabilization of keratolysis with arrest of corneal melting and merits further study. © 2013 Contact Lens Association of Ophthalmologists.


Kanan Y.,The University of Oklahoma Health Sciences Center | Kanan Y.,McGee Eye Institute | Matsumoto H.,The University of Oklahoma Health Sciences Center | Song H.,West Virginia University | And 5 more authors.
Journal of Neurochemistry | Year: 2010

In our previous studies, we have shown that insulin receptor (IR) activation leads to the activation of phosphoinositide 3-kinase (PI3K) and Akt activation in rod photoreceptors. This pathway is functionally important for photoreceptor survival as deletion of IR and one of the isoforms of Akt (Akt2) resulted in stress-induced photoreceptor degeneration. However, the molecular mechanism of this degeneration is not known. Akt signaling is known to be regulated by the serine/threonine phosphatases, PH domain and leucine-rich repeat protein phosphatases (PHLPP) and PHLPP-like (PHLPPL). In this study, we characterized these two phosphatases in the retina and examined the role of IR, PI3K, and Akt signaling on the activity of PHLPP and PHLPPL. Most of the studies published on PHLPP and PHLPPL are directed toward Akt dephosphorylation; however, there are no studies available to date on how the enzyme activities of these phosphatases are regulated. We made a novel finding in this study that both PHLPP and PHLPPL activities were significantly decreased in the presence of insulin ex vivo. The insulin-induced decrease of phosphatase activities were PI3K-dependent as pre-treatment of ex vivo retinal cultures with LY294002 significantly reversed the insulin-induced inhibition. It has been shown previously that PHLPP and PHLPPL regulate the dephosphorylation of Akt isoforms, and our results demonstrate for the first time that retinal PHLPP and PHLPPL activities are under the control of the IR-activated PI3K/Akt pathway. © 2010 International Society for Neurochemistry.


Logan S.,The University of Oklahoma Health Sciences Center | Logan S.,McGee Eye Institute | Agbaga M.-P.,The University of Oklahoma Health Sciences Center | Agbaga M.-P.,McGee Eye Institute | And 6 more authors.
Journal of Lipid Research | Year: 2014

Autosomal dominant Stargardt-like macular dystrophy (STGD3) in humans results from mutations in elongation of very long chain FAs-like 4 ( ELOVL4 ), which leads to vision loss in young adults. ELOVL4 is an integral endoplasmic reticulum (ER) protein that mediates the elongation of very long chain (VLC) FAs. Mutations in ELOVL4 lead to truncation and mislocalization of the translated protein from the ER, the site of FA elongation. Little is known about the enzymatic elongation of VLC-FAs by ELOVL4. We overexpressed full-length mouse ELOVL4, an N-glycosylationdeficient mutant, an ER-retention mutant, and mutants of active site histidines to parse their individual roles in VLC-FA elongation. ELOVL4 elongated appropriate precursors to the corresponding VLC-FA species ≥ 28 carbons. Active site histidine mutants of ELOVL4 did not elongate appropriate precursors, establishing ELOVL4 as the elongase. Displacing ELOVL4 from the ER was sufficient to cause loss of condensation activity, while absence of N-glycosylation was irrelevant for enzyme function. This study shows that ELOVL4 enzymatic activity is governed by individual histidines in its active site and the ER microenvironment, both of which are essential for elongation of VLC-FAs. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.


Siatkowski R.M.,McGee Eye Institute | Yanovitch T.L.,Duke University | Ash J.D.,McGee Eye Institute | Moreau A.,McGee Eye Institute
Journal of AAPOS | Year: 2011

Purpose: To determine the effect of intraperitoneal and intravitreal D-penicillamine (DPA) on retinal neovascularization in a murine model of oxygen-induced retinopathy. Methods: On postnatal day 7, 16 mice were injected intraperitoneally with 300 mg/kg/day DPA for 3 days followed by 50 mg/kg/day for 7 days. A different group of 7 mice were injected intraperitoneally with 600 mg/kg/day DPA for 3 days followed by 100 mg/kg/day for 7 days. A third group of 14 mice were injected with 1,500 mg/kg/day DPA for 2 days; a control cohort of 17 mice received intraperitoneal phosphate-buffered saline (PBS). An additional 15 mice underwent intravitreal injection of 1 μL of 100 mg/mL DPA in the right eye and 1 μL PBS intravitreally in the left eye as a control. All groups were placed in a 75% oxygen chamber for 7 days then room air for 3 days before being sacrificed and enucleated. The retinas were stained and flat-mounted to determine the severity of retinal neovascularization by quantifying neovascular buds. Results: After intraperitoneal injection, the mean number of glomeruli and tubules was similar in the DPA and PBS groups (P = 1.0), regardless of DPA dosage. The dosage of 1,500 mg/kg/day proved to be uniformly lethal. After intravitreal injections, the mean number of glomeruli (P = 0.16) and tubules (P = 0.7) were similar in the DPA and PBS groups. Conclusions: Neither intraperitoneal nor intravitreal injection of DPA inhibits retinal neovascularization in a murine model of oxygen-induced retinopathy. Copyright © 2011 Published by Elsevier Inc. on behalf of American Association for Pediatric Ophthalmology and Strabismus.


Gupta V.K.,The University of Oklahoma Health Sciences Center | Gupta V.K.,McGee Eye Institute | Rajala A.,The University of Oklahoma Health Sciences Center | Rajala A.,McGee Eye Institute | And 3 more authors.
EMBO Reports | Year: 2010

Growth factor receptor-bound protein 14 (Grb14) is an adaptor protein that is involved in receptor tyrosine kinase signalling. In this study, we report that Grb14 interacts with the rod photoreceptor-specific cyclic-nucleotide-gated channel alpha subunit (CNGA1) and decreases its affinity for cyclic guanosine monophosphate. Channel modulation is controlled by direct binding of the Grb14 Ras-associating domain with the carboxy-terminal region of CNGA1. We observed that the channel remains open in Grb14-mice that are exposed to light, suggesting that Grb14 is a normal physiological modulator of CNG channel function in vivo. © 2010 European Molecular Biology Organization.


Zulliger R.,The University of Oklahoma Health Sciences Center | Naash M.I.,The University of Oklahoma Health Sciences Center | Rajala R.V.S.,The University of Oklahoma Health Sciences Center | Rajala R.V.S.,McGee Eye Institute | And 3 more authors.
Journal of Biological Chemistry | Year: 2015

One-fifth of all cases of Leber congenital amaurosis are type 1 (LCA1). LCA1 is a severe form of retinal dystrophy caused by loss-of-function mutations in guanylate cyclase 1 (GC1), a key member of the phototransduction cascade involved in modulating the photocurrents. Although GC1 has been studied for some time, the mechanisms responsible for its regulation and membrane targeting are not fully understood. We reported earlier that retinal degeneration 3 (RD3) protein interacts with GC1 and promotes its targeting to the photoreceptor outer segments (POS). Here, we extend our studies to show a direct association between RD3 and guanylate cyclase activating protein 1 (GCAP1). Furthermore, we demonstrate that this functional interaction is important for GC1 targeting to POS. We also show that most LCA1-causing mutations in GC1 result in lost GC1 interaction with RD3 or GC1 being targetedtothe plasma membrane. Our data suggest that GC1, GCAP1, and RD3 form a complex in the endoplasmic reticulum that targets GC1 to POS. Interruption of this assembly is likely the underlying mechanism for a subset of LCA1. This study offers insights for the development of therapeutic strategies to treat this severe form of blindness. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

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