ROHTO NITTEN Co., Ltd.

This study compared intraocular toxicity of intravitreally injected povidone-iodine (PI) and polyvinyl alcohol-iodine (PAI) in rabbits.

In each rabbit, 0.1 mL of PI or PAI solution was injected intravitreally into one eye and saline was injected into the other. PI was tested at available iodine concentrations of 0.05%, 0.1%, 0.2%, and 0.5%, and PAI at 0.05%, 0.1%, and 0.2% (n = 6 each). Electroretinograms were recorded before injection and 1, 7, and 14 days after injection. Pathological examinations of eyeballs were performed on day 15.

Mean b-/a-wave ratios of the electroretinograms did not change in eyes injected with 0.05%, 0.1%, or 0.2% PI (PI-0.05, PI-0.1, and PI-0.2, respectively) or in eyes injected with 0.05% or 0.1% PAI (PAI-0.05 and PAI-0.1, respectively) compared to saline-injected eyes, but was transiently impaired on day 1 in PAI-0.2 eyes. Histopathologically, no retinal abnormalities were observed in PI-0.05, PAI-0.05, or PAI-0.1 eyes. One PI-0.1 eye first showed localized inflammatory cell infiltration in the inferior retinal region. Two PI-0.2 eyes and one PAI-0.2 eye had retinal degeneration and inflammatory cell infiltration. In the PI-0.5 group, extensive inflammatory cell infiltration was observed in six eyes and inferior retinal detachment in five eyes.

PI and PAI have equivalent retinal toxicity profiles, and retinal toxicity first affects the inner retinal layer in the inferior region. The highest non-retinotoxic vitreous concentration is 0.0033% available iodine from intravitreal injection of PI or PAI containing 0.05% available iodine.

Low concentrations of PI or PAI can be used to wash the ocular surface during surgery or intravitreal injection to prevent endophthalmitis.

Fibronectin plays an important role in the migration of corneal epithelial cells in vivo. The Arg-Gly-Asp (RGD) sequence in the principal cell binding domain of fibronectin mediates the interaction of fibronectin with integrins, whereas the Pro-His-Ser-Arg-Asn (PHSRN) sequence of fibronectin is thought to modulate this interaction. The authors examined the effects of a PHSRN peptide on corneal epithelial migration in vitro and in vivo.

Epithelial migration in vitro was examined with the rabbit cornea in organ culture. The motility and phenotype of simian virus 40-transformed human corneal epithelial (HCE) cells were evaluated by time-lapse and immunofluorescence microscopy, respectively. Tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin was examined by immunoprecipitation and immunoblot analysis. The healing of rabbit corneal epithelial wounds induced by 1-heptanol was evaluated by fluorescein staining.

The PHSRN peptide stimulated corneal epithelial migration in organ culture in a concentration-dependent manner, and it increased HCE cell motility in vitro. The peptide induced the accumulation of F-actin and the formation of focal adhesions at the leading edge of HCE cells. It also upregulated the tyrosine phosphorylation of FAK and paxillin in HCE cells, but it did not affect HCE cell proliferation or attachment to a fibronectin matrix. Administration of the PHSRN peptide in eye drops promoted corneal epithelial wound closure in vivo in a dose-dependent manner. None of these effects of the PHSRN peptide were induced by a control NRSHP peptide.

The PHSRN peptide mimics many of the effects of fibronectin on corneal epithelial cells and may prove suitable as a substitute for fibronectin in the treatment of persistent corneal epithelial defects.