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1.
Clin Ophthalmol ; 15: 2759-2766, 2021.
Article in English | MEDLINE | ID: mdl-34211265

ABSTRACT

PURPOSE: To describe the frequency and type of eye injuries in fighters in mixed martial arts (MMA) competition. METHODS: Fight result data were collected from the Nevada Athletic Commission database from 2001 to 2020. Any fighters in a professional mixed martial arts (MMA) contest with an eye injury were included. Main outcome measures included frequency and rate of eye injuries per fight and the types of eye injuries. Secondary outcome measures were gender, laterality, decision type, and length of no-contact recommended. RESULTS: Of the 256 MMA events in the database, 187 events (73.3%) had at least one eye injury. Of a total 2208 fights at these events, there were 363 fighters who sustained 369 eye injuries, with the yearly rate of eye injuries per 100 fighters ranging from 2.56 to 12.22. The most common injuries were eyebrow and eyelid lacerations (n=160, 43%), lacerations around the eye (n=98, 27%), and orbital fractures (n=62, 17%). Most eye injuries were right sided (n=197, 53.3%) and the majority of fighters with eye injuries lost their match (n=228, 62.8%). Fifty-seven fighters were recommended for further ophthalmology clearance after the match. The most common reasons for recommended ophthalmology follow-up was orbital fracture (n=25, 44%) and retinal injury (n=7, 12%). Forty-three fighters received no-contact requirements relating to their injury for an average of 8.9 weeks (range 1-24 weeks). CONCLUSION: Ophthalmic injuries in professional MMA were prevalent, were most often lacerations surrounding the eye, and often accompanied the fighter losing their match.

2.
Exp Eye Res ; 206: 108493, 2021 05.
Article in English | MEDLINE | ID: mdl-33596441

ABSTRACT

Current strategies to address corneal surface defects are insufficient to successfully resolve damage caused by injury and/or disease. To address this issue, we have developed an ocular wound chamber (OWC) that creates a fluid-filled environment by encompassing damaged ocular and periocular tissues allowing for the continuous delivery of therapeutics. This study tested human platelet lysate (hPL) as a treatment for corneal epithelial defects when used with the OWC. Corneal epithelial injuries were created in anesthetized guinea pigs by debridement of the central cornea. An OWC was placed over the injured eye and animals randomly grouped followed by injection of either 20% hPL, 100% hPL, or vehicle (balanced salt solution, BSS) into the chamber. Eyes were assessed at 0, 24, 48, and 72 h using intraocular pressure (IOP), optical coherence tomography (OCT), and fluorescein imaging. Whole globes were histologically processed, and hematoxylin and eosin (H&E) stained. No differences in IOP were recorded as a result of corneal wounding, chamber placement, and/or therapeutic application. OCT images demonstrated increased corneal swelling at 48 h and 72 h in the vehicle group compared to 20% hPL. Fluorescein staining showed increased corneal re-epithelialization in the 20% and 100% hPL groups at 48 h compared to vehicle only. H&E staining revealed increased stromal cellular infiltrate in the BSS group. This study demonstrates the delivery of hPL via the OWC improves corneal re-epithelialization and supports the expanded usage of the chamber in combination with hPL to manage a variety of corneal surface injuries, diseases and/or periocular conditions.


Subject(s)
Blood Platelets/metabolism , Corneal Injuries/therapy , Epithelium, Corneal/injuries , Re-Epithelialization/physiology , Wound Healing , Animals , Corneal Injuries/pathology , Epithelium, Corneal/pathology , Humans , Tomography, Optical Coherence
3.
J Burn Care Res ; 42(5): 1023-1025, 2021 09 30.
Article in English | MEDLINE | ID: mdl-33528572

ABSTRACT

An 18-year-old woman developed Stevens-Johnson syndrome (SJS) with ocular involvement after taking ibuprofen. She was admitted to another hospital, received saline flushes and bacitracin ophthalmic ointment to the eyes, and became unable to open them. Upon transfer to this burn center 3 weeks after symptom onset, there was complete fusion of both eyelids with no visible cornea or sclera. She underwent bilateral operative scar release. After opening the lids, meticulous debridement of cicatricial membranes and release of symblephara were performed with subsequent placement of amniotic membrane grafts. Her vision slowly improved, though her long-term visual prognosis remains guarded. Early recognition and treatment of SJS or toxic epidermal necrolysis (TEN) with ocular involvement is imperative. Even mild cases may require intensive topical lubrication, steroids, and antibiotics, with early placement of amniotic membrane grafts in severe cases. Prompt intervention and daily evaluation are paramount in preventing lifelong visual disability.


Subject(s)
Eyelid Diseases/surgery , Eyelids/surgery , Stevens-Johnson Syndrome/complications , Eyelid Diseases/etiology , Female , Humans , Stevens-Johnson Syndrome/surgery , Treatment Outcome , Visual Acuity/physiology , Young Adult
4.
J Biomater Appl ; 35(6): 592-601, 2021 01.
Article in English | MEDLINE | ID: mdl-32873118

ABSTRACT

Amniotic membrane (AM) has been shown to enhance corneal wound healing due to the abundance of growth factors, cytokines, and extracellular matrix (ECM) proteins inherent to the tissue. As such, AM has garnered widespread clinical utility as a biological dressing for a number of ophthalmic and soft tissue applications. The preparation, sterilization, and storage procedures used to manufacture AM grafts are extremely important for the conservation of inherent biological components within the membrane. Current processing techniques use harsh chemicals and sterilization agents that can compromise the fundamental wound healing properties of AM. Furthermore, commercially available cryopreserved AM products require specific storage conditions (e.g., ultra-low freezers) thereby limiting their clinical availability in austere environments. Supercritical carbon dioxide (SCCO2) technology allows for the sterilization of biological tissues without the resulting degradation of integral ECM proteins and other factors often seen with current tissue sterilization processes. With this study we demonstrate that lyophilized AM, sterilized using SCCO2, maintains similar biochemical properties and biocompatibility as that of commercially available AM products requiring specialized cold storage conditions.


Subject(s)
Allografts/chemistry , Amnion/chemistry , Biocompatible Materials/chemistry , Carbon Dioxide/chemistry , Freeze Drying/methods , Allografts/metabolism , Amnion/metabolism , Animals , Bandages , Biocompatible Materials/metabolism , Collodion/chemistry , Cornea/metabolism , Cytokines/metabolism , Extracellular Matrix/metabolism , Humans , Intercellular Signaling Peptides and Proteins/metabolism , Male , Rabbits , Sterilization , Wound Healing/drug effects
5.
Transl Vis Sci Technol ; 9(12): 4, 2020 11.
Article in English | MEDLINE | ID: mdl-33200046

ABSTRACT

Purpose: To demonstrate that the ocular wound chamber (OWC) can be used for the treatment of bacterial keratitis (BK). Methods: A blepharotomy was performed on anesthetized, hairless guinea pigs to induce exposure keratopathy 72 hours before corneal wound creation and Pseudomonas aeruginosa inoculation. Twenty-four hours postinoculation, eyes were treated with an OWC filled with 500 µL 0.5% moxifloxacin hydrochloride ophthalmic solution (OWC), 10 µL 0.5% moxifloxacin hydrochloride drops (DROPS) four times daily, or not treated (NT). White light, fluorescein, and spectral domain optical coherence tomography (SD-OCT) images; ocular and periocular tissues samples for colony-forming units (CFU) quantification; and plasma samples were collected at 24 and 72 hours posttreatment. Results: White light, fluorescein, and SD-OCT imaging suggests OWC-treated eyes are qualitatively healthier than those in DROPS or NT groups. At 24 hours, the median number of CFUs (interquartile range) measured was 0 (0-8750), 150,000 (106,750-181,250), and 8750 (2525-16,000) CFU/mL for OWC, NT, and DROPS, respectively. While 100% of NT and DROPS animals remained infected at 24 hours, only 25% of OWC-treated animals showed infection. Skin samples at 24 hours showed infection percentages of 50%, 75%, and 0% in DROPS, NT, and OWC groups, respectively. OWC-treated animals had higher moxifloxacin plasma concentrations at 24 and 72 hours than those treated with drops. Conclusions: OWC use resulted in a more rapid decrease of CFUs when compared to DROPS or NT groups and was associated with qualitatively healthier ocular and periocular tissue. Translational Relevance: The OWC could be used clinically to continuously and rapidly deliver antimicrobials to infected ocular and periocular tissues, effectively lowering bacterial bioburdens and mitigating long-term complications.


Subject(s)
Eye Infections, Bacterial , Eye Injuries , Keratitis , Animals , Eye Infections, Bacterial/drug therapy , Guinea Pigs , Keratitis/drug therapy , Moxifloxacin/therapeutic use , Pseudomonas aeruginosa
6.
Wound Repair Regen ; 26(5): 351-358, 2018 09.
Article in English | MEDLINE | ID: mdl-29943888

ABSTRACT

Current therapies available to treat and heal ocular surface injuries and periocular burns are frequently inadequate, costly, and labor intensive. To address these limitations, we have employed a flexible, semitransparent ocular wound chamber (OWC) to provide protection as well as a watertight seal to allow for the constant delivery of therapeutics to the ocular surface and surrounding periocular tissue. This study demonstrates the safety and utilization of the OWC on uninjured eyes and in our exposure keratopathy model. For initial safety studies (N = 3 per group), the eyelids remained intact and the eye uninjured. A blepharotomy (N = 6 per group) was performed to remove the upper and lower eyelids surrounding the left (OS) eye to create our exposure keratopathy model. Right (OD) eyes served as uninjured controls in all studies. Following OWC placement, 0.5 mL HPMC gel or balanced saline solution (BSS) was injected into the chamber. Animals were monitored daily and fully assessed via white light, fluorescein, and OCT imaging at least through 72 hours post OWC placement. In studies that included a blepharotomy, skin samples were analyzed by multiplex cytokine analysis. Results of safety experiments revealed no significant differences between treatment groups in corneal thickness, fluorescein staining, OCT imaging, or histological eye or skin sections when compared to control eyes. In our exposure keratopathy model, OWC treated eyes showed significantly less fluorescein uptake and also were found to have significantly lower levels of cytokines IL-13 and IL-5 in skin samples. These results demonstrate for the first time that treatment using the OWC device is not only safe, but significantly protects against blepharotomy-induced exposure keratopathy. As a whole, this study advances our overall efforts to develop a feasible solution to treat ocular surface injuries, infections, and periocular burns.


Subject(s)
Corneal Diseases/prevention & control , Eye Injuries/prevention & control , Eyelids/surgery , Wound Healing/physiology , Animals , Disease Models, Animal , Eyelids/injuries , Female , Guinea Pigs
7.
Clin Ophthalmol ; 12: 903-911, 2018.
Article in English | MEDLINE | ID: mdl-29785086

ABSTRACT

PURPOSE: Currently available ocular moisture chambers are not adequate to manage the treatment of periocular burns, corneal injuries, and infection. The purpose of these studies was to demonstrate that a flexible, semi-transparent ocular wound chamber device adapted from technology currently used on dermal wounds is safe for use on corneal epithelial injuries. MATERIALS AND METHODS: A depilatory cream (Nair™, 30 seconds) was utilized to remove the excess hair surrounding the left eyes of anesthetized Institute Armand Frappier (IAF) hairless, female guinea pigs (Crl:HA-Hrhr). A 4 mm corneal epithelium defect was created using a corneal rust ring remover (Algerbrush®II). Epithelial defects were either left untreated or the eyes were fitted with an ocular wound chamber and 0.5 mL of hydroxypropyl methylcellulose (HPMC) gel (GenTeal®) or HPMC liquid (GenTeal®) was injected into each chamber (N=5 per group). At 0, 24, 48, and 72 hours fluorescein and optical coherence tomography imaging was collected and the intraocular pressure (IOP) was measured. H&E staining was performed on corneal and eyelid skin samples and evaluated by a veterinary pathologist. RESULTS: Corneal epithelial wounds demonstrated 100% closure rates when left untreated or treated with an ocular wound chamber containing HPMC gel at 72 hours while wounds treated with an ocular wound chamber containing HPMC liquid were 98% healed. No significant differences were found in corneal thickness and wound healing, IOP, or eyelid skin pathology in any treatment group when compared to controls. CONCLUSIONS: This study indicates that adapted wound chamber technology can be safely used on sterile, corneal epithelial wounds without adverse effects on periocular or ocular tissue when filled with a liquid or gel.

8.
Burns ; 44(5): 1179-1186, 2018 08.
Article in English | MEDLINE | ID: mdl-29429747

ABSTRACT

PURPOSE: The study objective was to test the utilization of a crosslinked, thiolated hyaluronic acid (CMHA-S) film for treating corneal chemical burns. METHODS: Burns 5.5mm in diameter were created on 10 anesthetized, male New Zealand white rabbits by placing a 1N NaOH soaked circular filter paper onto the cornea for 30s. Wounds were immediately rinsed with balanced salt solution (BSS). CMHA-S films were placed in the left inferior fornix of five injured and five uninjured animals. Five animals received no treatment. At 0h, 48h, 96h, and on day 14 post chemical burn creation, eyes were evaluated by white light imaging, fluorescein staining, and optical coherence tomography (OCT). Corneal histology was performed using H&E and Masson's Trichrome stains. RESULTS: Image analysis indicated biocompatible CMHA-S treatment resulted in significant decreases in the areas of corneal opacity at 48h, 96h, and on day 14 postoperatively. A significant increase in re-epithelialization was seen 14days post injury. CMHA-S treated corneas showed significantly less edema than untreated burns. No pathological differences were observed in corneal histological samples as a result of CMHA-S treatment. CONCLUSIONS: CMHA-S films facilitate re-epithelialization and decrease the area of corneal opacity in our corneal alkali burn rabbit model.


Subject(s)
Burns, Chemical/drug therapy , Cornea/drug effects , Corneal Injuries/drug therapy , Eye Burns/drug therapy , Hyaluronic Acid/pharmacology , Re-Epithelialization/drug effects , Sulfhydryl Compounds/pharmacology , Viscosupplements/pharmacology , Alkalies/toxicity , Animals , Caustics/toxicity , Cornea/diagnostic imaging , Cornea/pathology , Corneal Edema , Corneal Injuries/chemically induced , Corneal Opacity , Disease Models, Animal , Epithelium, Corneal/drug effects , Eye Burns/chemically induced , Intravital Microscopy , Male , Microscopy, Confocal , Rabbits , Sodium Hydroxide/toxicity , Tomography, Optical Coherence
9.
Cornea ; 37(2): 211-217, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29140861

ABSTRACT

PURPOSE: Watertight closure of perforating corneoscleral lacerations is necessary to prevent epithelial ingrowth, infection, and potential loss of the eye. Complex lacerations can be difficult to treat, and repair with sutures alone is often inadequate. In this study, we evaluated a potentially sutureless technology for sealing complex corneal and scleral lacerations that bonds the amniotic membrane (AM) to the wound using only green light and rose bengal dye. METHODS: The AM was impregnated with rose bengal and then sealed over lacerations using green light to bond the AM to the deepithelialized corneal surface. This process was compared with suture repair of 3 laceration configurations in New Zealand White rabbits in 3 arms of the study. A fourth study arm assessed the side effect profile including viability of cells in the iris, damage to the blood-retinal barrier, retinal photoreceptors, retinal pigment epithelium, and choriocapillaris in Dutch Belted rabbits. RESULTS: Analyses of the first 3 arms revealed a clinically insignificant increase in polymorphonuclear inflammation. In the fourth arm, iris cells appeared unaffected and no evidence of breakdown of the blood-retinal barrier was detected. The retina from green light laser-treated eyes showed normal retinal pigment epithelium, intact outer segments, and normal outer nuclear layer thickness. CONCLUSIONS: The results of these studies established that a light-activated method to cross-link AM to the cornea can be used for sealing complex penetrating wounds in the cornea and sclera with minimal inflammation or secondary effects.


Subject(s)
Amnion/transplantation , Corneal Injuries/surgery , Fluorescent Dyes/therapeutic use , Lacerations/surgery , Photochemotherapy/methods , Rose Bengal/therapeutic use , Scleral Diseases/surgery , Animals , Disease Models, Animal , Lasers, Solid-State/therapeutic use , Rabbits , Sclera/injuries
10.
Mil Med ; 181(5 Suppl): 232-9, 2016 05.
Article in English | MEDLINE | ID: mdl-27168578

ABSTRACT

The corneal endothelium is paramount to the health and function of the cornea as damage to this cell layer can lead to corneal edema, opacification, and ultimately vision loss. Transplantation of the corneal endothelium is associated with numerous limitations, including graft rejection, thus an alternative therapeutic treatment is needed to restore endothelial layer integrity. We hypothesize that a nanotechnology-based approach using superparamagnetic iron oxide nanoparticles (SPIONPs) can ultimately be used to guide corneal endothelial cells (CECs) to injured areas via an external magnetic force without changing their morphology or viability. In this feasibility study we examined the effects of SPIONPs on the morphology and viability of bovine CECs in the presence of a magnetic force. The CECs were exposed to increasing SPIONP concentrations and the viability and cytoskeletal structure assessed over 3 days via metabolic analysis and rhodamine phalloidin staining. Significant differences (p < .05) in the metabolic activity of the CECs (100 × 10(6) SPIONP/cell) occurred in the presence of magnetic force versus those with no magnetic force. No differences were observed in the cytoskeleton of CECs in the presence or absence of magnetic force for all SPIONP concentrations. These SPIONPs will next be evaluated with human CECs for future applications.


Subject(s)
Corneal Endothelial Cell Loss/therapy , Endothelium, Corneal/surgery , Magnetite Nanoparticles/therapeutic use , Animals , Cattle/immunology , Cell Survival/drug effects , Cell Survival/immunology , Endothelium, Corneal/drug effects , Humans , Magnetite Nanoparticles/administration & dosage , Wound Healing/drug effects
11.
Ocul Surf ; 14(2): 168-88, 2016 04.
Article in English | MEDLINE | ID: mdl-26882981

ABSTRACT

Our purpose is to comprehensively review the state of the art with regard to Stevens- Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with particular attention to improving the management of associated ocular surface complications. SJS and TEN are two ends of a spectrum of immune-mediated disease, characterized in the acute phase by a febrile illness followed by skin and mucous membrane necrosis and detachment. Part I of this review focused on the systemic aspects of SJS/TEN and was published in the January 2016 issue of this journal. The purpose of Part II is to summarize the ocular manifestations and their management through all phases of SJS/TEN, from acute to chronic. We hope this effort will assist ophthalmologists in their management of SJS/TEN, so that patients with this complex and debilitating disease receive the best possible care and experience the most optimal outcomes in their vision and quality of life.


Subject(s)
Stevens-Johnson Syndrome , Epidermis , Eye Diseases , Humans , Necrosis , Quality of Life , Skin
12.
Ocul Surf ; 14(1): 2-19, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26549248

ABSTRACT

The intent of this review is to comprehensively appraise the state of the art with regard to Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with particular attention to the ocular surface complications and their management. SJS and TEN represent two ends of a spectrum of immune-mediated, dermatobullous disease, characterized in the acute phase by a febrile illness followed by skin and mucous membrane necrosis and detachment. The widespread keratinocyte death seen in SJS/TEN is rapid and irreversible, and even with early and aggressive intervention, morbidity is severe and mortality not uncommon. We have divided this review into two parts. Part I summarizes the epidemiology and immunopathogenesis of SJS/TEN and discusses systemic therapy and its possible benefits. We hope this review will help the ophthalmologist better understand the mechanisms of disease in SJS/TEN and enhance their care of patients with this complex and often debilitating disease. Part II (April 2016 issue) will focus on ophthalmic manifestations.


Subject(s)
Disease Management , Ophthalmology/methods , Practice Guidelines as Topic , Stevens-Johnson Syndrome/therapy , Humans
13.
Clin Exp Ophthalmol ; 43(3): 239-46, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25112787

ABSTRACT

BACKGROUND: The incidence of blast-induced ocular injury has dramatically increased due to advances in weaponry and military tactics. A single exposure to blast overpressure (BOP) has been shown to cause damage to the eye in animal models; however, on the battlefield, military personnel are exposed to BOP multiple times. The effects of repeated exposures to BOP on ocular tissues have not been investigated. The purpose of this study is to characterize the effects of single or repeated exposure on ocular tissues. METHODS: A compressed air shock tube was used to deliver 70 ± 7 KPa BOP to rats, once (single blast overpressure [SBOP]) or once daily for 5 days (repeated blast overpressure [RBOP]). Immunohistochemistry was performed to characterize the pathophysiology of ocular injuries induced by SBOP and RBOP. Apoptosis was determined by quantification activated caspase 3. Gliosis was examined by detection of glial fibrillary acidic protein (GFAP). Inflammation was examined by detection of CD68. RESULTS: Activated caspase 3 was detected in ocular tissues from all animals subjected to BOP, while those exposed to RBOP had more activated caspase 3 in the optic nerve than those exposed to SBOP. GFAP was detected in the retinas from all animals subjected to BOP. CD68 was detected in optic nerves from all animals exposed to BOP. CONCLUSION: SBOP and RBOP induced retinal damage. RBOP caused more apoptosis in the optic nerve than SBOP, suggesting that RBOP causes more severe optic neuropathy than SBOP. SBOP and RBOP caused gliosis in the retina and increased inflammation in the optic nerve.


Subject(s)
Air Pressure , Blast Injuries/physiopathology , Disease Models, Animal , Eye Injuries/physiopathology , Gliosis/physiopathology , Optic Nerve Injuries/physiopathology , Retina/injuries , Animals , Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/metabolism , Apoptosis , Blast Injuries/metabolism , Caspase 3/metabolism , Eye Injuries/metabolism , Glial Fibrillary Acidic Protein/metabolism , Gliosis/metabolism , Immunoenzyme Techniques , Male , Optic Nerve Injuries/metabolism , Rats , Rats, Long-Evans
14.
Mil Med ; 179(8 Suppl): 34-40, 2014 Aug.
Article in English | MEDLINE | ID: mdl-25102547

ABSTRACT

BACKGROUND: Blast-induced ocular trauma is a frequent cause of morbidity for survivors of improvised explosive devices. Blast overpressure (BOP) of 120 ± 7 KPa has been shown to cause damage to lungs, brain, and gut in a rat model; however, the effects of BOP on ocular tissues have not been characterized. To elucidate the pathophysiology of blast-induced ocular trauma, ocular tissues from rats subjected to blast were examined for evidence of apoptosis by the detection of activated caspase 3 and TUNEL assay in their ocular tissues. METHODS: A compressed air shock tube was used to deliver 120 ± 7 KPa of BOP for duration of 2 msec to the right side of the rats. Rats were then euthanized at specific time points after blast exposure (3 hours, 24 hours, 48 hours). Ocular tissues were processed for immunohistochemistry to detect activated caspase 3 and TUNEL assay. Tissues were evaluated for relative levels of positive signal as compared to nonblast exposed controls. RESULTS: Activated caspase 3 was detected in the optic nerve, ganglion layer, and inner nuclear layer post blast exposure. At 24 and 48 hours, the inner nuclear layer from the right side had more cells with activated caspase 3. In the optic nerve, the highest levels of activated caspase 3 were detected on the right side at 24 hours post blast. CONCLUSION: BOP of 120 ± 7 KPa induces optic neuropathy and retinal damage. In both the optic nerve and retina, caspase 3 was activated in the right and left sides following blast exposure. The results of this study reveal that blast exposure induces apoptosis in both the optic nerve and retinal tissues.


Subject(s)
Blast Injuries/physiopathology , Eye Injuries/physiopathology , Optic Nerve Injuries/physiopathology , Retina/injuries , Animals , Apoptosis , Caspase 3/analysis , Male , Optic Nerve Injuries/metabolism , Rats , Rats, Sprague-Dawley , Retina/chemistry
15.
Invest Ophthalmol Vis Sci ; 55(1): 198-209, 2014 Jan 09.
Article in English | MEDLINE | ID: mdl-24255038

ABSTRACT

PURPOSE: Retinal pigmented epithelium derived from human induced pluripotent stem (iPS) cells (iPS-RPE) may be a source of cells for transplantation. For this reason, it is essential to determine the functional competence of iPS-RPE. One key role of the RPE is uptake and processing of retinoids via the visual cycle. The purpose of this study is to investigate the expression of visual cycle proteins and the functional ability of the visual cycle in iPS-RPE. METHODS: iPS-RPE was derived from human iPS cells. Immunocytochemistry, RT-PCR, and Western blot analysis were used to detect expression of RPE genes lecithin-retinol acyl transferase (LRAT), RPE65, cellular retinaldehyde-binding protein (CRALBP), and pigment epithelium-derived factor (PEDF). All-trans retinol was delivered to cultured cells or whole cell homogenate to assess the ability of the iPS-RPE to process retinoids. RESULTS: Cultured iPS-RPE expresses visual cycle genes LRAT, CRALBP, and RPE65. After incubation with all-trans retinol, iPS-RPE synthesized up to 2942 ± 551 pmol/mg protein all-trans retinyl esters. Inhibition of LRAT with N-ethylmaleimide (NEM) prevented retinyl ester synthesis. Significantly, after incubation with all-trans retinol, iPS-RPE released 188 ± 88 pmol/mg protein 11-cis retinaldehyde into the culture media. CONCLUSIONS: iPS-RPE develops classic RPE characteristics and maintains expression of visual cycle proteins. The results of this study confirm that iPS-RPE possesses the machinery to process retinoids for support of visual pigment regeneration. Inhibition of all-trans retinyl ester accumulation by NEM confirms LRAT is active in iPS-RPE. Finally, the detection of 11-cis retinaldehyde in the culture medium demonstrates the cells' ability to process retinoids through the visual cycle. This study demonstrates expression of key visual cycle machinery and complete visual cycle activity in iPS-RPE.


Subject(s)
Eye Proteins/genetics , Gene Expression Regulation , Nerve Growth Factors/genetics , RNA/genetics , Retinal Pigment Epithelium/metabolism , Retinoids/metabolism , Serpins/genetics , Vision, Ocular/genetics , Blotting, Western , Cells, Cultured , Eye Proteins/biosynthesis , Humans , Immunohistochemistry , Nerve Growth Factors/biosynthesis , Real-Time Polymerase Chain Reaction , Retinal Pigment Epithelium/cytology , Serpins/biosynthesis
16.
Invest Ophthalmol Vis Sci ; 52(13): 9470-7, 2011 Dec 09.
Article in English | MEDLINE | ID: mdl-22058339

ABSTRACT

PURPOSE: Suturing amniotic membrane to cornea during surgery is time consuming, and sutures may further damage the eye. The authors introduce a novel sutureless, light-activated technique that securely attaches amnion to cornea through protein-protein crosslinks. METHODS: Cryopreserved human amniotic membrane, stained with Rose Bengal (RB), was placed over a full-thickness wound in deepithelialized rabbit cornea and was treated with green laser. The intraocular pressure that broke the seal (IOP(L)) was measured, and adhesion was measured with a peel test. The influences on bonding strength of fluence, irradiance, RB concentration, and amnion surface bonded were measured. Epithelial cell migration on treated amnion and keratocyte viability after bonding were also measured. The involvement in the bonding mechanism of oxygen, singlet oxygen, and association of RB with stromal collagen was investigated. RESULTS: Sealing amniotic membrane over cornea using 0.1% RB and 150 J/cm(2) at 532 nm produced an IOP(L) of 261 ± 77 mm Hg ex vivo and 448 mm ± 212 mm Hg in vivo. The ex vivo IOP(L) increased with increasing fluence (50-150 J/cm(2)). Equivalent IOP(L) was produced for bonding basement membrane or stromal amnion surfaces. The bonding treatment was not toxic to keratocytes but slightly reduced the migration of corneal epithelial cells on amnion ex vivo. Mechanism studies indicated that RB forms two complexes with amnion stromal collagen, that bonding requires oxygen, and that singlet oxygen mediates protein crosslinking. CONCLUSIONS: A rapid, light-activated technique produces strong, immediate bonding between amnion and cornea and merits further evaluation for ocular surface surgeries.


Subject(s)
Amnion/transplantation , Cornea/surgery , Corneal Diseases/surgery , Animals , Cell Movement , Corneal Diseases/pathology , Cryopreservation , Disease Models, Animal , Epithelium, Corneal/pathology , Humans , Laser Therapy , Rabbits , Treatment Outcome
17.
PLoS One ; 6(10): e24832, 2011.
Article in English | MEDLINE | ID: mdl-21998632

ABSTRACT

Smallpox, caused by variola virus (VARV), is a devastating human disease that affected millions worldwide until the virus was eradicated in the 1970 s. Subsequent cessation of vaccination has resulted in an immunologically naive human population that would be at risk should VARV be used as an agent of bioterrorism. The development of antivirals and improved vaccines to counter this threat would be facilitated by the development of animal models using authentic VARV. Towards this end, cynomolgus macaques were identified as adequate hosts for VARV, developing ordinary or hemorrhagic smallpox in a dose-dependent fashion. To further refine this model, we performed a serial sampling study on macaques exposed to doses of VARV strain Harper calibrated to induce ordinary or hemorrhagic disease. Several key differences were noted between these models. In the ordinary smallpox model, lymphoid and myeloid hyperplasias were consistently found whereas lymphocytolysis and hematopoietic necrosis developed in hemorrhagic smallpox. Viral antigen accumulation, as assessed immunohistochemically, was mild and transient in the ordinary smallpox model. In contrast, in the hemorrhagic model antigen distribution was widespread and included tissues and cells not involved in the ordinary model. Hemorrhagic smallpox developed only in the presence of secondary bacterial infections - an observation also commonly noted in historical reports of human smallpox. Together, our results support the macaque model as an excellent surrogate for human smallpox in terms of disease onset, acute disease course, and gross and histopathological lesions.


Subject(s)
Disease Progression , Macaca fascicularis/virology , Smallpox/pathology , Variola virus/pathogenicity , Animals , Body Temperature , Body Weight , Female , Hematologic Tests , Kinetics , Male , Smallpox/blood , Smallpox/physiopathology , Smallpox/transmission , Viremia/pathology
18.
Cornea ; 29(7): 833-5, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20489592

ABSTRACT

PURPOSE: To report a case of a spontaneous subconjunctival abscess in a patient with no previous ocular surgery or trauma. METHOD: Case report. RESULTS: We report a case of a subconjunctival abscess caused by Haemophilus influenzae after several days of worsening conjunctivitis. Computed tomography scans of the orbits confirmed an abscess cavity adjacent to the globe without orbital extension. The abscess was spontaneously draining at presentation and resolved completely with topical and oral antibiotic therapy. CONCLUSIONS: To our knowledge, this is the first-described case of spontaneous subconjunctival abscess formation in an immunocompetent individual unrelated to preexisting ocular pathology, previous ocular surgery, or trauma. H. influenzae species may possess the ability to penetrate an intact conjunctiva and develop subconjunctival abscess. We recommend that patients presenting with bacterial conjunctivitis be closely examined to rule out subconjunctival abscess, which may require additional aggressive medical or surgical management.


Subject(s)
Abscess/microbiology , Conjunctival Diseases/microbiology , Eye Infections, Bacterial/microbiology , Haemophilus Infections/microbiology , Haemophilus influenzae/isolation & purification , Abscess/diagnosis , Abscess/drug therapy , Adult , Anti-Infective Agents/therapeutic use , Aza Compounds/therapeutic use , Conjunctival Diseases/diagnosis , Conjunctival Diseases/drug therapy , Drug Therapy, Combination , Eye Infections, Bacterial/diagnosis , Eye Infections, Bacterial/drug therapy , Female , Fluoroquinolones , Haemophilus Infections/diagnosis , Haemophilus Infections/drug therapy , Humans , Moxifloxacin , Quinolines/therapeutic use , Tobramycin/therapeutic use , Tomography, X-Ray Computed , Vancomycin/therapeutic use
20.
Ophthalmology ; 115(2): 377-82, 2008 Feb.
Article in English | MEDLINE | ID: mdl-17904224

ABSTRACT

PURPOSE: To document the incidence and treatment of patients with severe ocular and ocular adnexal injuries during Operation Iraqi Freedom. DESIGN: Retrospective hospital-based observational analysis of injuries. PARTICIPANTS: All coalition forces, enemy prisoners of war, and civilians with severe ocular and ocular adnexal injuries. METHODS: The authors retrospectively examined severe ocular and ocular adnexal injuries that were treated by United States Army ophthalmologists during the war in Iraq from March 2003 through December 2005. MAIN OUTCOME MEASURES: Incidence, causes, and treatment of severe ocular and ocular adnexal injuries. RESULTS: During the time data were gathered, 797 severe eye injuries were treated. The most common cause of the eye injuries was explosions with fragmentation injury. Among those injured, there were 438 open globe injuries, of which 49 were bilateral. A total of 116 eyes were removed (enucleation, evisceration, or exenteration), of which 6 patients required bilateral enucleation. Injuries to other body systems were common. CONCLUSIONS: Severe eye injuries represent a significant form of trauma encountered in Operation Iraqi Freedom. These injuries were most commonly caused by explosion trauma.


Subject(s)
Eye Injuries, Penetrating/epidemiology , Eyelids/injuries , Iraq War, 2003-2011 , Military Personnel , Orbit/injuries , Adult , Blast Injuries/epidemiology , Explosions/statistics & numerical data , Eye Enucleation , Eye Evisceration , Eye Foreign Bodies/epidemiology , Eye Injuries, Penetrating/etiology , Eye Injuries, Penetrating/surgery , Female , Hospitals, Military , Humans , Incidence , Male , Ophthalmology , Retrospective Studies , United States
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