Inflammatory responses after vitrectomy with vitreous substitutes in a rabbit model

Abstract

Purpose To investigate the inflammatory response of current and future potential vitreous substitutes in an experimental in vivo vitrectomy model. Methods Twenty-five gauge pars plana vitrectomy was performed in the right eye of 60 pigmented rabbits, with subsequent injection of 0.5-1.0 ml of Healaflow® (cross-linked hyaluronic acid, n = 12), Bio-Alcamid® (polyalkylimide, n = 8), silicone oil (n = 12), or balanced saline solution (BSS, n = 28). Postoperative clinical evaluation was performed; and the rabbits were sacrificed at 1 day, 1 week, or 1 month. The eyecups were then examined macroscopically; the retinas sectioned and stained with hematoxylin and eosin (Htx), and immunohistochemically labeled for glial fibrillary acidic protein (GFAP), CD45, galectin-3, CD68, and CD20. Unoperated left eyes from treated animals as well as eyes from untreated animals were used as controls. Results Vitrectomy without major complications was achieved in 46/60 eyes. The remaining 14 eyes were analyzed separately. One eye developed endophthalmitis after 1 week and was excluded. Eyes treated with Healaflow®, silicone oil, and BSS had a comparable appearance macroscopically and in Htx-stained sections, whereas Bio-Alcamid®-injected eyes exhibited increased macroscopic inflammation and severely affected retinas. GFAP upregulation was present in all treatment groups, most prominent in eyes treated with Bio-Alcamid® and silicone oil. Upregulation of CD45 and CD68 in the inner retina and vitreous space was most prominent with Bio-Alcamid® treatment, and these eyes together with their silicone oil-treated counterparts also displayed a stronger upregulation of CD20-labeled cells compared with remaining groups. General upregulation of galectin-3, mainly in the inner retina, was found in all groups. In eyes with perioperative complications, labeling of CD45, CD68, and especially GFAP was comparably high. Conclusions We here describe differences in the postsurgery inflammatory profiles of existing and potential vitreous substitutes. Bio-Alcamid® and silicone oil display severe signs of gliosis and inflammation, whereas Healaflow® elicits minimal reactions comparable with BSS, highlighting its potential application as a vitreous substitute in a future clinical setting.

A New Retinal Detachment Treatment Model for Evaluation of Vitreous Tamponades

“…In previous studies using HF in normal eyes, we found no signs of excessive inflammation. 13,14 The fact that 2/8 HF filled eyes in the present study developed this complication after repeat surgery indicates that the tamponading gel may induce different tissue reactions within a pathological environment. This is also highlighted by the one repeat surgery HF eye in which severe retinal degeneration in an attached area was noted.…”

“…We have previously described models for studying various vitreous substitutes in vitro and in vivo. [10][11][12][13][14] A new potential vitreous substitutecross-linked hyaluronic acid hydrogel, Healaflow® (HF) -in these experiments has been found to exhibit excellent biocompatibility in vitro as well as in normal rabbit eyes in vivo.…”

Macro- and Microscale Properties of the Vitreous Humor to Inform Substitute Design and Intravitreal Biotransport

“…A big discrepancy in the number of publications on hydrogel vitreous substitutes and vitreous humor in the years 1995-2000 (9 publications and 0 publications, respectively) should be noted, considering the approval of silicone oil for use as a vitreous substitute by the Food and Drug Administration (FDA) in 1994. 58 Synthetic 33,34,59-91 and semisynthetic [92][93][94][95][96][97][98][99][100][101][102][103][104][105][106][107][108] hydrogels have been more common materials for experimental vitreous substitutes in recent years, while natural hydrogels 37,[109][110][111][112][113][114][115][116][117][118][119][120][121][122][123] were much more prevalent in the early years ( Figure 3B). The foldable capsular vitreous body (FCVB) is a different polymeric design for a vitreous substitute that is currently undergoing clinical trials in China.…”

New epiretinal implant with integrated sensor chips for optical capturing shows a good biocompatibility profile in vitro and in vivo

“…Moreover, a pressure-induced retinal atrophy was observed due to the lack-based fixation process. However, the immunohistological results proved that there was no significant increase in CD45-positive cells, meaning no immigration of inflammatory cells into the retina as immune reaction [28]. Therefore, we can assume that further improvements in the design of such structures are necessary, but that they are fundamentally suitable for stimulating the retina and enable new ways of transmitting signals and energy into a retinal implant.…”