The effect of recombinant human hyaluronidase on dexamethasone penetration into the posterior segment of the eye after sub-Tenon's injection.
OBJECTIVE
The aim of this study was to investigate the extent if recombinant human hyaluronidase (rhuPH20) can enhance trans-scleral penetration of sub-Tenon's dexamethasone (DM) into the posterior segment of the eye.


METHODS
rhuPH20 was purified from conditioned media through a series of ion exchange, hydrophobic interaction, aminophenylboronate, and hydroxyapatite chromatography to greater than 90% purity based upon specific activity. Only the right eye of each rabbit was injected. The first group (n = 16) received an injection of DM and rhuPH20, whereas the second group (n = 16) received DM only. The eyes were enucleated 1, 2, 3, and 6 h after the injection, and the choroid, retina, vitreous, aqueous, and serum were harvested. DM concentration was assessed by mass spectrometry. Histology (n = 2) and immunohistochemistry (n = 2) was performed to detect toxicity and the presence of the rHuPH20, respectively.


RESULTS
We observed no histopathologic damage to ocular tissues after sub-Tenon's injection. This enzyme significantly increased DM level in the choroid and the retina 3 h after administration. The rise in levels was transient returning to normal levels by 6 h.


CONCLUSIONS
Sub-Tenon's coinjection of rHuPH20 with DM resulted in a general increase in DM levels in ocular tissues and the serum, with significant increase in the choroid and the retina, 3 h after administration.
Kozak
Igor
I
Jacobs Retina Center at the Shiley Eye Center, University of California-San Diego, La Jolla, CA 92037, USA.
Kayikcioglu
Ozcan R
OR
Cheng
Lingyun
L
Falkenstein
Iryna
I
Silva
Gabriel A
GA
Yu
Diana X
DX
Freeman
William R
WR
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D003907:Dexamethasone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004338:Drug Combinations; D004347:Drug Interactions; D005123:Eye / Q000378:metabolism*; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000494:pharmacology*; D007267:Injections; D010539:Permeability / Q000187:drug effects; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D004338:Drug Combinations; D011994:Recombinant Proteins; D003907:Dexamethasone; D006821:Hyaluronoglucosaminidase