Biosynthetic Corneal Substitute Implantation in Dogs

Abstract

Purpose To assess integration of a biosynthetic corneal implant in dogs. Methods Three normal adult laboratory Beagles underwent ophthalmic examinations, including slit-lamp biomicroscopy, indirect ophthalmoscopy, applanation tonometry, and Cochet–Bonnet aesthesiometry. Biosynthetic corneas fabricated from glutaraldehyde crosslinked collagen and copolymers of collagen and poly (N-isopropylacrylamide-co-acrylic acid-co-acryloxysuccinimide, denoted as TERP) were implanted into dogs by a modified epikeratoplasty technique. Ophthalmic examinations and aesthesiometry were performed daily for 5 days and then weekly thereafter for 16 weeks. Corneal samples underwent histopathological and transmission electron microscopy examination at 16 weeks. Results Implants were epithelialized by 7 days. Intraocular pressure was within normal range throughout the study. Aesthesiometry values dropped from an average of 3.67 cm preoperatively to less than 1 mm for all dogs for the first postoperative weeks. By week 16, the average Cochet–Bonnet value was 1.67 cm, demonstrating partial recovery of functional innervation of the implant. No inflammation or rejection of the implant occurred, and minimal haze formation was noted. Light microscopy revealed thickened but normal epithelium over the implant with fibroblast migration into the scaffold. On transmission electron microscopy, the basement membrane was irregular but present and adhesion complexes were noted. Conclusion Biosynthetic corneal implantation is well tolerated in dogs, and the collagen–polymer hybrid construct holds promise for clinical application in animals and humans.

Biodegradable Glutaraldehyde‐crosslinked Casein Conduit Promotes Regeneration after Peripheral Nerve Injury in Adult Rats

“…The non‐invasive real‐time NF‐ κ B bioluminescence imaging accompanied with histochemical assessment also showed the GCC was highly biocompatible, only evoking a mild tissue response. These results are not surprising since casein has been shown as a promising material for use in drug delivery,46 and glutaraldehyde has shown prominent cross‐linking capability for artificial organs including bones, corneas, skins, and nerves 47–50…”

Biodegradable Glutaraldehyde‐crosslinked Casein Conduit Promotes Regeneration after Peripheral Nerve Injury in Adult Rats

“…The non‐invasive real‐time NF‐ κ B bioluminescence imaging accompanied with histochemical assessment also showed the GCC was highly biocompatible, only evoking a mild tissue response. These results are not surprising since casein has been shown as a promising material for use in drug delivery,46 and glutaraldehyde has shown prominent cross‐linking capability for artificial organs including bones, corneas, skins, and nerves 47–50…”

In Vivo Imaging of Corneal Endothelial Dystrophy in Boston Terriers: A Spontaneous, Canine Model for Fuchs' Endothelial Corneal Dystrophy

“…First, naturally occurring diseases such as CED in BTs likely better reflect the complex environmental, genetic, and physiological variation present within the human population versus the highly uniform genetic background and homogenous environment characteristic of laboratory animals. 46 Second, dogs are commonly used to investigate corneal diseases 47 , 48 as well as for surgical interventions and outcomes especially with regard to keratoprosthetics 49 due to their similar corneal anatomy in comparison to humans, relatively large eyes, and ease of handling in the laboratory. Endothelial injury models have been described in the rabbit, primate, and cat using transcorneal freezing, 50 , 51 or surgical removal.…”

Phenotypic Characterization of Corneal Endothelial Dystrophy in German Shorthaired and Wirehaired Pointers Using In Vivo Advanced Corneal Imaging and Histopathology

“…29 Dogs are commonly used in ocular drug development and to investigate and develop treatments for corneal disease due to their large eyes, ease of handling, and relatively similar corneal anatomy to humans. 30–32 There are well characterized murine FECD models, Col8a2 L450W/L450W and Col8a2 Q455K/Q455K , which exhibit guttae, decreased ECD and altered endothelial cell morphology 33 but these models have limited value for investigating surgical and cell-based interventions due to the small murine eye. Additionally, a large discrepancy exists between murine and human CCT likely contributing to great variability in the kinetics of topical ocular drug delivery between the two species.…”

Biodegradable Glutaraldehyde‐crosslinked Casein Conduit Promotes Regeneration after Peripheral Nerve Injury in Adult Rats

“…The non‐invasive real‐time NF‐ κ B bioluminescence imaging accompanied with histochemical assessment also showed the GCC was highly biocompatible, only evoking a mild tissue response. These results are not surprising since casein has been shown as a promising material for use in drug delivery,46 and glutaraldehyde has shown prominent cross‐linking capability for artificial organs including bones, corneas, skins, and nerves 47–50…”

In Vivo Imaging of Corneal Endothelial Dystrophy in Boston Terriers: A Spontaneous, Canine Model for Fuchs' Endothelial Corneal Dystrophy

“…First, naturally occurring diseases such as CED in BTs likely better reflect the complex environmental, genetic, and physiological variation present within the human population versus the highly uniform genetic background and homogenous environment characteristic of laboratory animals. 46 Second, dogs are commonly used to investigate corneal diseases 47 , 48 as well as for surgical interventions and outcomes especially with regard to keratoprosthetics 49 due to their similar corneal anatomy in comparison to humans, relatively large eyes, and ease of handling in the laboratory. Endothelial injury models have been described in the rabbit, primate, and cat using transcorneal freezing, 50 , 51 or surgical removal.…”

Phenotypic Characterization of Corneal Endothelial Dystrophy in German Shorthaired and Wirehaired Pointers Using In Vivo Advanced Corneal Imaging and Histopathology

“…29 Dogs are commonly used in ocular drug development and to investigate and develop treatments for corneal disease due to their large eyes, ease of handling, and relatively similar corneal anatomy to humans. 30–32 There are well characterized murine FECD models, Col8a2 L450W/L450W and Col8a2 Q455K/Q455K , which exhibit guttae, decreased ECD and altered endothelial cell morphology 33 but these models have limited value for investigating surgical and cell-based interventions due to the small murine eye. Additionally, a large discrepancy exists between murine and human CCT likely contributing to great variability in the kinetics of topical ocular drug delivery between the two species.…”

Biodegradable Glutaraldehyde‐crosslinked Casein Conduit Promotes Regeneration after Peripheral Nerve Injury in Adult Rats

“…The non‐invasive real‐time NF‐ κ B bioluminescence imaging accompanied with histochemical assessment also showed the GCC was highly biocompatible, only evoking a mild tissue response. These results are not surprising since casein has been shown as a promising material for use in drug delivery,46 and glutaraldehyde has shown prominent cross‐linking capability for artificial organs including bones, corneas, skins, and nerves 47–50…”

In Vivo Imaging of Corneal Endothelial Dystrophy in Boston Terriers: A Spontaneous, Canine Model for Fuchs' Endothelial Corneal Dystrophy

“…First, naturally occurring diseases such as CED in BTs likely better reflect the complex environmental, genetic, and physiological variation present within the human population versus the highly uniform genetic background and homogenous environment characteristic of laboratory animals. 46 Second, dogs are commonly used to investigate corneal diseases 47 , 48 as well as for surgical interventions and outcomes especially with regard to keratoprosthetics 49 due to their similar corneal anatomy in comparison to humans, relatively large eyes, and ease of handling in the laboratory. Endothelial injury models have been described in the rabbit, primate, and cat using transcorneal freezing, 50 , 51 or surgical removal.…”

Phenotypic Characterization of Corneal Endothelial Dystrophy in German Shorthaired and Wirehaired Pointers Using In Vivo Advanced Corneal Imaging and Histopathology

“…29 Dogs are commonly used in ocular drug development and to investigate and develop treatments for corneal disease due to their large eyes, ease of handling, and relatively similar corneal anatomy to humans. 30–32 There are well characterized murine FECD models, Col8a2 L450W/L450W and Col8a2 Q455K/Q455K , which exhibit guttae, decreased ECD and altered endothelial cell morphology 33 but these models have limited value for investigating surgical and cell-based interventions due to the small murine eye. Additionally, a large discrepancy exists between murine and human CCT likely contributing to great variability in the kinetics of topical ocular drug delivery between the two species.…”