Gonçalves E Souza Lenara, Vilardo Lóes Moreira Matheus, Sayuri Saçaki Claudia, Perlmann Eduardo, Guimarães Lopes Thacyana Beatriz, Ferreira Enio, Moreno Juan Carlos Duque, Montiani-Ferreira Fabiano
Veterinary Medicine, Department, Rua dos Funcionarios, Graduate School of Veterinary Sciences, Federal University of Parana, Curitiba, Brazil.
Laboratory of Veterinary Pathology, MVL Patologia Veterinária, Belo Horizonte, Brazil.
Front Vet Sci. 2024 Jul 24;11:1415658. doi: 10.3389/fvets.2024.1415658. eCollection 2024.
Corneal ulcers are common lesions in both human and veterinary medicine. However, only a few studies have evaluated the efficacy of cross-linked hyaluronic acid (X-HA) eye drops on corneal wound healing. To our knowledge, this is the first study to demonstrate and compare the efficacy of amniotic membrane extract eye drops (AMEED) and X-HA for corneal wound healing in rats.
A total of 15 male Wistar rats (30 eyes) were used in this study. Then, 10 eyes were treated with X-HA, AMEED, or 0.9% saline. After general and topical anesthesia, a superficial corneal ulcer was created using a corneal trephine. The defect was further polished with a diamond burr. Three groups of 10 eyes each were treated with either one drop of 0.75% X-HA or AMEED or 0.9% saline (control), administered every 12 h for a duration of 72 h. The median epithelial defect area (MEDA), expressed as a percentage of the total corneal surface, was measured at 0, 12, 24, 36, 48, and 72 h. Re-epithelization time scores were also evaluated. The Kruskal-Wallis test was used to compare median times for re-epithelization and histopathologic scores between groups, while the Friedman test (for paired data) was employed to compare results from the serial analysis of MEDA and vascularization scores between groups.
MEDA was not significantly different between X-HA and AMEED. However, MEDA was significantly smaller in the X-HA group compared to the control group at 36 h (2.73 interquartile range (IQR) 5.52% x 9.95 IQR 9.10%, P=0.024) and 48 h (0.00 IQR 0.26% x 6.30 IQR 8.54%, P=0.030). The overall time for re-epithelization was significantly lower in the X-HA group (3.00 IQR 3.00) compared to the AMEED (6.5 IQR 3.00) and control (7.00 IQR 1.00) groups (P=0.035). Vascularization, hydropic degeneration, and epithelial-stromal separation were significantly less observed in samples in the X-HA-treated compared to samples in the AMEED- and saline-treated groups. Significantly more corneal epithelium cells were labeled for caspase3 in samples from the AMEED- and saline-treated groups compared to those from the X-HA-treated group.
Topical X-HA has been shown to accelerate corneal epithelial healing. AMEED did not decrease corneal re-epithelialization time. X-HA may also potentially be used as an adjunct therapy for treating corneal ulcers in clinical situations.
角膜溃疡在人类医学和兽医学中都是常见病症。然而，仅有少数研究评估了交联透明质酸（X-HA）滴眼液对角膜伤口愈合的疗效。据我们所知，这是第一项证明并比较羊膜提取物滴眼液（AMEED）和X-HA对大鼠角膜伤口愈合疗效的研究。
本研究共使用15只雄性Wistar大鼠（30只眼）。然后，10只眼分别用X-HA、AMEED或0.9%生理盐水进行治疗。在全身麻醉和局部麻醉后，使用角膜环钻制作一个浅表角膜溃疡。缺损处再用金刚石磨头进行打磨。三组，每组10只眼，分别每12小时滴一滴0.75%的X-HA或AMEED或0.9%生理盐水（对照组），持续72小时。在0、12、24、36、48和72小时测量以角膜总表面积百分比表示的中位上皮缺损面积（MEDA）。还评估了再上皮化时间评分。采用Kruskal-Wallis检验比较各组之间的再上皮化中位时间和组织病理学评分，而采用Friedman检验（用于配对数据）比较各组之间MEDA和血管化评分的系列分析结果。
X-HA组和AMEED组之间的MEDA无显著差异。然而，与对照组相比，X-HA组在36小时（2.73四分位间距（IQR）5.52%×9.95 IQR 9.10%，P = 0 . 024）和48小时（0.00 IQR 0.26%×6.30 IQR 8.54%，P = 0 . 030）时的MEDA显著更小。与AMEED组（6.5 IQR 3.00）和对照组（7.00 IQR 1.00）相比，X-HA组的总体再上皮化时间显著更低（3.00 IQR 3.00）（P = 0 . 035）。与AMEED组和生理盐水处理组的样本相比，X-HA处理组的样本中观察到的血管化、水样变性和上皮-基质分离显著更少。与X-HA处理组的样本相比，AMEED组和生理盐水处理组的样本中标记半胱天冬酶3的角膜上皮细胞显著更多。
局部应用X-HA已被证明可加速角膜上皮愈合。AMEED并未缩短角膜再上皮化时间。X-HA在临床情况下也可能潜在地用作治疗角膜溃疡的辅助疗法。
