Biomedical subjects

Christopher J Murphy

Publications and source records attributed to Christopher J Murphy.

At least 19 recordsLinked to original sources

PubMed2007

The effect of trophic factor supplementation on cold ischemia-induced early apoptotic changes.

We have previously shown that trophic factor supplementation (TFS) of University of Wisconsin (UW) solution enhanced kidney viability after cold storage. Here, we use an in vitro model to study the effect of TFS on early apoptotic changes after cold ischemic storage. Mitochondrial membrane potential was determined by fluorescence intensity in primary canine kidney tubule cells, Madin-Darby canine kidney cells, and human umbilical vein endothelial cells. In addition, caspase 3 enzyme activity assay and immunofluorescence staining were performed to evaluate apoptosis. There was a 15% increase in mitochondrial membrane potential in human umbilical vein endothelial cells stored in trophic factor supplemented University of Wisconsin solution after four-hour rewarming (P<0.05). TFS suppressed caspase 3 enzyme activity and activation in human umbilical vein endothelial cells. We confirmed that the presence of TFS in UW solution has a beneficial effect by protecting mitochondrial function and reducing early apoptotic changes in vascular endothelial cells.

Animals↗

PubMed2006

Development of a retrobulbar injection technique for ocular surgery and analgesia in dogs.

OBJECTIVE: To develop and compare 3 techniques for retrobulbar injection of local anesthetic agents for ocular surgery and analgesia in dogs. DESIGN: Prospective study. ANIMALS: 17 dogs (including 9 cadavers). PROCEDURES: Inferior-temporal palpebral (ITP), perimandibular, and combined superior-inferior peribulbar injection techniques were compared by assessing the distribution of latex after injection into the orbits of 5 canine cadavers; magnetic resonance imaging (MRI) evaluation of the distribution of contrast agent after injection in the retrobulbar space of 4 canine cadavers; and assessment of the efficacy and MRI evaluation of the anatomic distribution of injections of a lidocainecontrast agent mixture in 4 anesthetized, nonrecovery dogs. By use of the preferred technique (ITP), the ocular effects of lidocaine anesthesia were evaluated in 4 dogs; during a 2-week period after treatment, dogs underwent ophthalmic examination, Schirmer tear testing (STT), intraocular pressure (IOP) measurement, and Cochet-Bonnet esthesiometry. RESULTS: Of the 3 techniques, the ITP technique was the preferred method for retrobulbar administration of anesthetic agent in dogs because it was efficacious (pupil dilation and central rotation of the globe achieved in all eyes), easiest to perform, and provided thorough coverage of the intraconal retrobulbar space without complication. During the 2-week follow-up period, the ITP injection did not significantly affect STT, IOP, or Cochet-Bonnet esthesiometry values in dogs. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, retrobulbar administration of anesthetic agents via the ITP technique is a potential alternative to systemic administration of neuromuscular blocking agents for ophthalmic surgery and provides the additional benefit of local ocular analgesia.

Analgesia↗

PubMed2006

A new method to characterize chemically and topographically nanopatterned surfaces.

Surface chemistry of topographically patterned grooved samples with ridges of 150 nm width, adsorbed with self-assembled monolayers (SAMs) of alkanethiols on gold, have been characterized by near edge X-ray absorption fine structure (NEXAFS) spectroscopy. Analysis reveals that NEXAFS may discriminate between different chemistries adsorbed to the tops, sidewalls and grooves of the patterns.

Coated Materials, Biocompatible↗

PubMed2006

The effect of environmental factors on the response of human corneal epithelial cells to nanoscale substrate topography.

We have previously shown that human corneal epithelial cells sense and react to nanoscale substrate topographic stimuli [Teixeira AI, Abrams GA, Bertics PJ, Murphy CJ, Nealey PF. Epithelial contact guidance on well-defined micro- and nanostructured substrates. J Cell Sci 2003;116(10):1881-92; Karuri NW, Liliensiek S, Teixeira AI, Abrams G, Campbell S, Nealey PF, et al. Biological length scale topography enhances cell-substratum adhesion of human corneal epithelial cells. J Cell Sci 2004;117(15):3153-64]. Here we demonstrate that cellular responses to nanoscale substrate topographies are modulated by the context in which these stimuli are presented to cells. In Epilife medium, cells aligned preferentially in the direction perpendicular to nanoscale grooves and ridges. This is in contrast to a previous study where cells cultured in DMEM/F12 medium aligned in the direction parallel to nanoscale topographic features [Teixeira AI, Abrams GA, Bertics PJ, Murphy CJ, Nealey PF. Epithelial contact guidance on well-defined micro- and nanostructured substrates. J Cell Sci 2003;116(10):1881-92]. Additionally, cell alignment in Epilife medium was dependent on pattern pitch. Cells switched from perpendicular to parallel alignment when the pitch was increased from 400 to 4,000 nm. There was a transition region (between 800 and 1,600 nm pitch) where both parallel and perpendicular alignments were favored compared to all other cellular orientations. Cells formed focal adhesions parallel to the substrate topographies in this transition region. On the nano- and microscale patterns, 400 and 4,000 nm pitch, focal adhesions were almost exclusively oriented obliquely to the topographic patterns.

Biocompatible Materials↗

PubMed2006

Cell sorting but not serum starvation is effective for SV40 human corneal epithelial cell cycle synchronization.

SV40 human corneal epithelial cell (HCEC) populations are readily used as a substitute for primary corneal epithelial cells that are difficult to maintain in vitro. To initiate cell-cycle experiments with the SV40-HCEC cells, two separate methods of cell synchronization were compared including serum starvation and sterile cell sorting. We hypothesized that SV40 cells are synchronized at higher efficiencies into each cell cycle phase (G1, S, G2M) when cell sorting is performed when compared to alternative methods of synchronization. SV40 cells were synchronized by deprivation of serum over 96 h or labeled with Höechst 33342 dye and sorted based on DNA content. Cells were synchronized using both methods and harvested at time points up to 72 h after release. To define more precisely the nature of sorted fractions, cells were pulsed with BrdU prior to sorting. SV40-HCEC cells exhibit a well-defined cell cycle profile. Serum deprivation up to 96 h was ineffective for cell synchronization of SV40-HCECs. In comparison, we achieved efficient synchronization of the SV40-HCECs with sterile cell sorting. SV40-HCEC cells gated into G1, S and G2M were synchronized up to 85% following the sort and maintained synchronization up to 24 h. Our findings indicate that serum starvation is not effective for synchronization of the SV40-HCEC cell line. We present a more effective approach, the use of cell sorting for cell synchronization of the SV40-HCEC cells.

Benzimidazoles↗

PubMed2006

Characterizing nanoscale topography of the aortic heart valve basement membrane for tissue engineering heart valve scaffold design.

A fully effective prosthetic heart valve has not yet been developed. A successful tissue-engineered valve prosthetic must contain a scaffold that fully supports valve endothelial cell function. Recently, topographic features of scaffolds have been shown to influence the behavior of a variety of cell types and should be considered in rational scaffold design and fabrication. The basement membrane of the aortic valve endothelium provides important parameters for tissue engineering scaffold design. This study presents a quantitative characterization of the topographic features of the native aortic valve endothelial basement membrane; topographical features were measured, and quantitative data were generated using scanning electron microscopy (SEM), atomic force microscopy (AFM), transmission electron microscopy (TEM), and light microscopy. Optimal conditions for basement membrane isolation were established. Histological, immunohistochemical, and TEM analyses following decellularization confirmed basement membrane integrity. SEM and AFM photomicrographs of isolated basement membrane were captured and quantitatively analyzed. The basement membrane of the aortic valve has a rich, felt-like, 3-D nanoscale topography, consisting of pores, fibers, and elevations. All features measured were in the sub-100 nm range. No statistical difference was found between the fibrosal and ventricular surfaces of the cusp. These data provide a rational starting point for the design of extracellular scaffolds with nanoscale topographic features that mimic those found in the native aortic heart valve basement membrane.

Animals↗

PubMed2006

Nano- and microscale holes modulate cell-substrate adhesion, cytoskeletal organization, and -beta1 integrin localization in SV40 human corneal epithelial cells.

Human corneal epithelial cells (HCECs) interface with a basement membrane in vivo that possesses complex nanoscale topographic features. We report that synthetic substrates patterned with nano- and microscale holes differentially modulate the proliferation, shape and adhesion of SV40 human corneal epithelial cells (SV40-HCECs) as a function of feature size: 1) Cell proliferation was inhibited on nanoscale features (features size less than 800 nm in pitch) compared to microscale features or planar substrates in identical culture conditions. 2) Cells on nanoscale holes had a stellate morphology compared to those on microscale features that were more evenly spread. 3) Cells adhered more to nanoscale features than to microscale features when exposed to shear stress in a laminar flow chamber. Transmission electron microscopy showed that cells cultured on the 400 nm pitch patterns had longer and more numerous filopodia and retraction fibers than cells cultured on the 1600 nm pitch patterns. Immunogold labeling of -beta1 integrins revealed that these receptors were localized at the cell periphery and in the aforementioned cytoskeletal elements. Our findings indicate that surface discontinuities and the activation of mechanochemical cell signaling mechanisms may contribute to the observed responses exhibited by SV40-HCECs cultured on nano- and microscale topography.

Cell Adhesion↗

PubMed2006

Evaluation of acoustic wave propagation velocities in the ocular lens and vitreous tissues of pigs, dogs, and rabbits.

OBJECTIVE: To evaluate propagation velocity of acoustic waves through the lens and vitreous body of pigs, dogs, and rabbits and determine whether there were associations between acoustic wave speed and age, temperature, and time after enucleation. SAMPLE POPULATION: 9 pig, 40 dog, and 20 rabbit lenses and 16 pig, 17 dog, and 23 rabbit vitreous bodies. PROCEDURE: Acoustic wave velocities through the ocular structures were measured by use of the substitution technique. RESULTS: Mean sound wave velocities in lenses of pigs, dogs, and rabbits were 1,681, 1,707, and 1,731 m/s, respectively, at 36 degrees C. Mean sound wave velocities in the vitreous body of pigs, dogs, and rabbits were 1,535, 1,535, and 1,534 m/s, respectively, at 38 degrees C. The sound wave speed through the vitreous humor, but not the lens, increased linearly with temperature. An association between wave speed and age was observed in the rabbit tissues. Time after enucleation did not affect the velocity of sound in the lens or vitreous body. The sound wave speed conversion factors for lenses, calculated with respect to human ocular tissue at 36 degrees C, were 1.024, 1.040, and 1.055 for pig, dog, and rabbit lenses, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Conversion factors for the speed of sound through lens tissues are needed to avoid underestimation of the thickness of the lens and axial length of the eye in dogs during comparative A-mode ultrasound examinations. These findings are important for accurate calculation of intraocular lens power required to achieve emmetropia in veterinary patients after surgical lens extraction.

Aging↗

PubMed2005

Putative aqueous humor misdirection syndrome as a cause of glaucoma in cats: 32 cases (1997-2003).

OBJECTIVE: To characterize the clinical and morphologic aspects of aqueous humor misdirection syndrome (AHMS) in cats and provide a hypothesis regarding its pathogenesis on the basis of detailed analysis of affected cats. DESIGN: Retrospective study. ANIMALS: 32 cats (40 eyes). PROCEDURE: Medical records of cats in which AHMS was diagnosed from July 1997 to August 2003 were reviewed. In certain cats, results of additional diagnostic testing were also obtained, including A-scan, B-scan, and high-resolution ultrasonography; streak retinoscopy; video keratometry; and infrared neutralizing videoretinoscopy as well as results of analysis of flash-frozen sections and histologic examination of enucleated globes. RESULTS: Cats had a uniformly shallow anterior chamber, intact lens zonules, and a narrowed approach to an open iridocorneal angle. Mean age of affected cats was 11.7 years (range, 4 to 16 years), and female cats were significantly more often affected than male cats. Clinical signs included mydriasis, decreased pupillary light reflex, decreased menace response, and blindness. Glaucomatous changes to the optic nerve, incipient cataracts, and eventual blindness were seen. Intraocular pressure was > or = 20 mm Hg (range, 12 to 58 mm Hg) in 32 of 40 eyes. Ultrasonography and histologic examination revealed a thickened anterior vitreal face interposed between the lens and ciliary body, partial ciliary cleft collapse, and cavitated vitreal regions. Various treatment modalities were used. CONCLUSIONS AND CLINICAL RELEVANCE: AHMS affects older cats, especially females, and may result in glaucoma, vision loss, and signs of ocular pain. Topical administration of carbonic anhydrase inhibitors decreased intraocular pressure.

Age Factors↗

PubMed2005

Nerve growth factor and corneal wound healing in dogs.

Nerve growth factor in the tear film and corneal epithelium is hypothesized to play an important role in ocular surface maintenance and corneal wound healing. The purpose of this study was to determine the expression of nerve growth factor and its high affinity (trkA) receptor in tears, cornea, and lacrimal glands of normal dogs, the modulation of nerve growth factor and its trkA receptor during corneal wound healing, and the effect of topical nerve growth factor application on canine corneal epithelial wound healing. In the first of three experiments, the nerve growth factor content of tears, corneal epithelium, lacrimal gland, and 3rd eyelid gland was determined in normal dogs by enzyme-linked immunosorbent assay and the expression of nerve growth factor and its trkA receptor were evaluated in the cornea and lacrimal glands by immunohistochemistry. In a second experiment, unilateral corneal epithelial defects were created, and tissues were evaluated for changes in nerve growth factor or trkA expression for 1 week. In a third experiment, bilateral corneal epithelial defects were created and the right eyes in each animal were treated 4 times daily with either recombinant human nerve growth factor, murine nerve growth factor, or nerve growth factor-blocking antibody. The results of this study showed that nerve growth factor levels in normal dog tears, corneal epithelium, third eyelid gland and lacrimal gland were 15.4+/-4.6 ng ml(-1), 33.5+/-12.3, 52.4+/-17.4 and 48.8+/-9.4 ng g(-1), respectively. NGF and trkA receptors were identified by immunohistochemistry in all tissues examined. After unilateral corneal wounding, nerve growth factor concentration increased in the tears bilaterally for 3 days, especially in the wounded eye, and then returned to pre-wounding values. Nerve growth factor content, and immunohistochemical staining for nerve growth factor and trkA, increased significantly in the ipsilateral cornea epithelium following unilateral wounding. Nerve growth factor concentrations in lacrimal and third eyelid glands also increased bilaterally (p<0.01) after unilateral wounding. Time to wound closure and rate of epithelial migration did not differ significantly between nerve growth factor-treated, nerve growth factor antibody-treated, and control eyes. In conclusion, nerve growth factor is present under resting physiologic conditions in normal canine tears, and nerve growth factor and its trkA receptor are present under resting conditions in normal canine corneal epithelium, lacrimal gland and third eyelid gland. Nerve growth factor is elevated in the tears, cornea, and lacrimal glands after corneal epithelial wounding; however, topical application of nerve growth factor, or its blocking antibody does not modulate corneal wound healing in the normal dog eye.

Animals↗

PubMed2005

Cooperative modulation of neuritogenesis by PC12 cells by topography and nerve growth factor.

Understanding axonal formation and contact guidance are of critical importance for the design of materials that interface with neuronal tissue. Contact guidance of neurites by topographic features is well known, but the role that topography plays in the modulation of neuritogenesis has not been addressed. To test this, we cultured PC12 cells with a range of nerve growth factor (NGF) concentrations on surfaces with ridge widths ranging from 70 to 1900 nm. We find that neuritogenesis by PC12 cells cultured with sub-optimal concentrations of NGF (25 and 5 ng/ml) is modulated by topographic feature size. The threshold for induction of neuritogenesis was markedly reduced when cells were cultured on ridges of 70 and 250 nm. In contrast, contact guidance of neurites was independent of feature size. These results suggest that the scale of topographic features can act cooperatively with NGF signaling to regulate the formation of neurites. These findings may have general relevance to differentiation processes in neurons as well as in other cell types.

Animals↗

PubMed2005

Compatibility of lyotropic liquid crystals with viruses and mammalian cells that support the replication of viruses.

We report a study that investigates the biocompatibility of materials that form lyotropic liquid crystals (LCs) with viruses and mammalian cells that support the replication of viruses. This study is focused on aqueous solutions of tetradecyldimethyl-amineoxide (C(14)AO) and decanol (D), or disodium cromoglycate (DSCG; C(23)H(14)O(11)Na(2)), which can form optically birefringent, liquid crystalline phases. The influence of these materials on the ability of vesicular stomatitis virus (VSV) to infect human epitheloid cervical carcinoma (HeLa) cells was examined by two approaches. First, VSV was dispersed in aqueous C(14)AO+ D or DSCG, and then HeLa cells were inoculated by contacting the cells with the aqueous C(14)AO + D or DSCG containing VSV. The infectivity of VSV to the HeLa cells was subsequently determined. Second, VSV was incubated in LC phases of either C(14)AO + D or DSCG for 4 h, and the concentration (titer) of infectious virus in the LC was determined by dilution into cell culture medium and subsequent inoculation of HeLa cells. Using these approaches, we found that the LC containing C(14)AO + D caused inactivation of virus as well as cell death. In contrast, we determined that VSV retained its infectivity in the presence of aqueous DSCG, and that greater than 74-82% of the HeLa cells survived contact with aqueous DSCG (depending on concentration of DSCG). Because VSV maintained its function (and we infer structure) in LCs formed from DSCG, we further explored the influence of the virus on the ordering of the LC. Whereas the LC formed from DSCG was uniformly aligned on surfaces prepared from self-assembled monolayers (SAMs) of HS(CH(2))(11)(OCH(2)CH(2))(4)OH on obliquely deposited films of gold in the absence of VSV, the introduction of 10(7)-10(8) infectious virus particles per milliliter caused the LC to assume a non-uniform orientation and a colorful appearance that was readily distinguished from the uniformly aligned LCs. Control experiments using cell lysates with equivalent protein concentrations but no virus did not perturb the uniform alignment of the LC.

Biocompatible Materials↗

PubMed2004

Responses of human keratocytes to micro- and nanostructured substrates.

We have previously shown that human corneal epithelial cells respond to synthetic topographic features with dimensions similar to those found in the native human corneal basement membrane. Epithelial cells integrated inputs from substrate topography and soluble factors in the culture medium to generate alignment responses to substrate topographic anisotropies. Human keratocytes are the main cellular components of the stroma, the tissue that underlies the corneal epithelium. Here we report that keratocytes aligned more strongly than epithelial cells along topographic patterns of grooves and ridges. On patterns with pitches of 800 nm and larger approximately 70% of keratocytes were aligned along the patterns compared to 35% for epithelial cells. On 70 nm-wide ridges on a 400-nm pitch, keratocyte alignment dropped to 45%, whereas epithelial cell alignment remained constant. Similarly to epithelial cells, focal adhesions and associated stress fibers in keratocytes were aligned mainly along the substrate topographies, although oblique orientations were also observed. Furthermore, keratocytes cultured on the nanoscale patterns had fewer stress fibers and focal adhesions than cells cultured on microscale patterns or on smooth substrates.

Cell Movement↗

PubMed2004

Biological length scale topography enhances cell-substratum adhesion of human corneal epithelial cells.

The basement membrane possesses a rich 3-dimensional nanoscale topography that provides a physical stimulus, which may modulate cell-substratum adhesion. We have investigated the strength of cell-substratum adhesion on nanoscale topographic features of a similar scale to that of the native basement membrane. SV40 human corneal epithelial cells were challenged by well-defined fluid shear, and cell detachment was monitored. We created silicon substrata with uniform grooves and ridges having pitch dimensions of 400-4000 nm using X-ray lithography. F-actin labeling of cells that had been incubated for 24 hours revealed that the percentage of aligned and elongated cells on the patterned surfaces was the same regardless of pitch dimension. In contrast, at the highest fluid shear, a biphasic trend in cell adhesion was observed with cells being most adherent to the smaller features. The 400 nm pitch had the highest percentage of adherent cells at the end of the adhesion assay. The effect of substratum topography was lost for the largest features evaluated, the 4000 nm pitch. Qualitative and quantitative analyses of the cells during and after flow indicated that the aligned and elongated cells on the 400 nm pitch were more tightly adhered compared to aligned cells on the larger patterns. Selected experiments with primary cultured human corneal epithelial cells produced similar results to the SV40 human corneal epithelial cells. These findings have relevance to interpretation of cell-biomaterial interactions in tissue engineering and prosthetic design.

Actins↗

PubMed2004

Improved survival of orthotopic liver allograft in swine by addition of trophic factors to University of Wisconsin solution.

Serum-free preservation media such as University of Wisconsin (UW) may cause tissue damage through trophic factor (TF) deprivation. This study evaluated whether the addition of TFs to UW solution improves liver graft quality after extended cold preservation time in pigs. UW solution was supplemented with epidermal growth factor, insulin-like growth factor-1, nerve growth factor-beta, bactenecin, and substance P to create TF-supplemented (TFS) UW. Orthotopic liver transplantation was performed after 18 hr of static cold storage at 4 degrees C in UW (n=7) or TFS-UW (n=7) solution. Recipients of grafts preserved with TFS-UW demonstrated significantly better 5-day survival (57%) than those preserved with UW alone (14%) (P<0.05). Adenosine triphosphate content in grafts preserved in TFS-UW was significantly higher than in grafts preserved in UW (17.4+/-5.0 vs. 4.8+/-1.2 nmol/mg protein, respectively) (P<0.05). This study showed that the addition of TFs to UW solution allowed a significant extension of cold ischemic time in pigs.

Adenosine↗

PubMed2004

Thermal cautery of the cornea for treatment of spontaneous chronic corneal epithelial defects in dogs and horses.

A thermal cautery technique was used to treat spontaneous chronic corneal epithelial defects (SCCEDs) in 9 eyes of 8 dogs and 2 eyes of 2 horses. Animals were sedated, and a topical anesthetic was applied. A handheld thermal cautery unit was then used to make multiple, small (< or = 1 mm in diameter), superficial burns throughout the affected area. The cautery unit was applied just until the slightest degree of contraction of the collagen fibrils was observed. After the stromal bed of the defect was treated, a rim of epithelium that extended approximately 1 mm around the denuded stroma was also subjected to thermal cautery. Following surgery, a contact lens was placed in dogs but not in horses, and the eye was treated with broad-spectrum antimicrobial ophthalmic solutions. Defects in all 11 eyes healed with minimal scarring; mean time to healing in dogs was 2.1 weeks (range, 2 to 3 weeks). The defect healed in 1 week in 1 horse and in 2 weeks in the other. Many therapeutic options are available for the treatment of SCCEDs. Procedures such as epithelial debridement and anterior stromal puncture have been shown to have a high rate of success. In cases for which these less invasive procedures fail, our results suggest that thermal cautery may be a reasonable alternative to previously described treatments for SCCEDs in dogs and horses prior to more invasive procedures such as superficial keratectomy.

Animals↗

PubMed2004

Suppression of cold ischemic injury in stored kidneys by the antimicrobial peptide bactenecin.

BACKGROUND: Cold ischemic injury plays an important role in short- and long-term function of kidneys after transplant. Antimicrobial peptides have not previously been studied for their impact on cold ischemia in transplanted kidneys. METHODS: Bactenecin (L- and D-forms) was added to University of Wisconsin (UW) preservation solution for 3-day cold storage of dog kidneys. Effects on membrane permeability were studied in synthetic liposomes and in kidney cortex tissue slices. The role of bactenecin as a tissue mitogen and direct cytoskeletal stabilizer were studied with cultured cells and in vitro. RESULTS: Bactenecin (both L- and D- forms) resulted in significant decreases in postoperative serum creatinine and time required for return of creatinine to the normal range showing the effect was independent of chirality. Bactenecin permeabilized synthetic liposomes and altered kidney cortex tissue slice membrane permeability characteristics, irrespective of chirality. Neither did bactenecin act as a mitogen for either primary renal tubule or Madin-Darby canine kidney (MDCK) cells stored in UW solution, nor did it appear to directly affect cytoskeletal dynamics. CONCLUSIONS: These results show that the antimicrobial peptide bactenecin can improve the quality of static cold storage of kidneys. The mechanism of its action is independent of receptor binding and does not appear to involve either an effect on the cytoskeleton or via activity as a mitogen. Current evidence best supports the hypothesis that bactenecin protects against cold ischemic injury by a controlled permeabilization of the membranes of the kidney during cold storage.

Actins↗

PubMed2004

Topical therapeutic agents that modulate corneal wound healing.

In summary, corneal wound healing is a complex phenomenon that involves interplay between the cellular elements of the cornea, numerous soluble factors, and the constituents of the ECM. Unfortunately, many studies that demonstrate marked alteration on cell behavior in vitro and even in in vivo experiments are often not helpful in the diseased patient, as shown by the results of careful clinical trials. Future work that addresses the complex milieu of the corneal wound healing environment by addressing the interaction of many of these factors will be more likely to be successful than seeking a single agent that will enhance wound healing in all situations. Modulation of wound healing processes by the application of topical therapeutic agents is, however, an expanding field of study sure to produce clinically significant improvements in the management of veterinary patients with corneal defects. The judicious use of topical cytoactive compounds has a place in the clinician's armamentarium integrated into a therapeutic plan that decreases the mechanical stresses imposed on the wound bed as well as removal of any underlying inciting cause.

Administration, Topical↗