Ex vivo permeation of erythropoietin through porcine conjunctiva, cornea, and sclera

Abstract

The aim of this study is to test the permeation of human recombinant erythropoietin (rHuEPO) across conjunctiva, cornea, and sclera in an ex vivo model. Thirty fresh pig eyes were collected from a slaughterhouse. Conjunctivas (n = 10), corneas (n = 10), and scleras (n = 10) were surgically dissected from surrounding tissues. Ocular membranes were placed into Franz diffusion cells and rHuEPO was administered into the donor phase of each cell, except for control samples. Samples were collected from the receptor phase at seven time points, from 30 min to 6 h of incubation. Erythropoietin (EPO) was quantified by enzyme-linked immunosorbent assay (ELISA) technique. Ocular membranes immunohistochemistry was also performed at the end of the study. EPO was detected in all test samples. After 6 h of incubation, conjunctiva was the most permeable membrane to rHuEPO (509.3 ± 89.8 mIU/cm, corresponding to 0.52% of the total rHuEPO administered on the donor phase), followed by sclera (359.1 ± 123.7 mIU/cm, corresponding to 0.35%) and finally cornea (71.0 ± 31.8 mIU/cm, corresponding to 0.07%). Differences between ocular membranes' permeation were statistically significant (p < 0.001). EPO immunostaining signal was positive for the three ocular membranes. We have demonstrated in an ex vivo model that porcine conjunctiva, cornea, and sclera are permeable to rHuEPO protein. These are promising results concerning ocular EPO administration.

Functional and Structural Effects of Erythropoietin Subconjunctival Administration in Glaucomatous Animals

“…They also concluded that scleral permeability decreased with increasing molecular weight and the molecular radius [22]. We have previously demonstrated that rHuEPO can permeate porcine conjunctiva, sclera, and corneas in an ex vivo model [30]. Since glaucoma is a chronic disease, multiple treatments to protect RGCs are required, and using the subconjunctival route seems to be more feasible.…”

Optimization, Biopharmaceutical Profile and Therapeutic Efficacy of Pioglitazone-loaded PLGA-PEG Nanospheres as a Novel Strategy for Ocular Inflammatory Disorders

“…The value of Jss of the PGZ in cornea and sclera were similar for free drug. The PGZ from NSs permeates less through the cornea than sclera, showing that the cornea has a barrier effect three times higher than the sclera (30). This is a consequence of the cornea having a regular cellular order, while the cells of the sclera have a more irregular cellular arrangement (31).…”

Potential effects of angiogenesis-related factors on the severity of APAC and surgical outcomes of trabeculectomy

“…The study is translational to clinical practice in that it reminds us that EPO therapy is a double-edged sword in the treatment of eye disease. Different modes of EPO administration, such as systemic delivery or intravitreal injection, have given positive results for ocular disorders [ 2 , 36 , 37 ]. There is emerging evidence for the neuroprotection effect of EPO both in vivo and in vitro [ 21 , 38 , 39 ].…”