Efficacy of retinol palmitate eye drops for dry eye in rabbits with lacrimal gland resection

Akito Odaka, Hiroshi Toshida, Toshihiko Ohta, Nobuhito Tabuchi, Daisuke Koike, Chikako Suto, Akira Murakami, Akito Odaka, Hiroshi Toshida, Toshihiko Ohta, Nobuhito Tabuchi, Daisuke Koike, Chikako Suto, Akira Murakami

Abstract

Purpose: We examined the efficacy of retinol palmitate (VApal) for dry eyes using dry eye model rabbits whose lacrimal glands were resected.

Materials and methods: After alkaline injury on keratoconjunctival epithelium, VApal eye drops were administered 6 times a day for 7 days. The efficacy of VApal was also compared with that of 0.1% hyaluronic acid eye drops.

Results: The fluorescein staining and rose bengal scores showed a significant decrease compared with the score in the vehicle group at 7 days (P < 0.05) in the 1000 IU/mL VApal group and at both 3 days (P < 0.05) and 7 days (P < 0.01) in the 1500 IU/mL VApal group. Histological examination revealed recovery of the corneal epithelium, and PAS staining disclosed the recovery of mucin-producing lower palpebral conjunctival goblet cells after 7 days in the 1500 IU/mL VApal group compared with the vehicle group. Results from impression cytology showed a significant increase in density of conjunctival goblet cells compared with that in the vehicle group after 7 days in the 1000 IU/mL VApal group and after 3 and 7 days in the 1500 IU/mL VApal group. There were no significant changes in tear flow in either group. Topical application of VApal at 1500 IU/mL showed greater improvement than 0.1% hyaluronic acid in both fluorescein and rose bengal score and in the density of conjunctival goblet cells.

Conclusion: It is suggested that VApal is effective for the improvement of keratoconjunctival epithelial damage associated with tear abnormalities, such as dry eyes.

Keywords: cornea; dry eye; hyaluronic acid; retinol palmitate; vitamin A; wound healing.

Figures

Figure 1
Figure 1
Slit-lamp microscopic images of fluorescein (A–D) and rose bengal (E–H) staining in rabbit eyes at 7 days of treatment with the VApal or the vehicle. Corneal findings stained with fluorescein in 500 IU/mL (B), 1000 IU/mL (C) and 1500 IU/mL (D) of VApal-treated eye and the vehicle-treated eye (A), stained with rose bengal in 500 IU/mL (F), 1000 IU/mL (G), and 1500 IU/mL (H) of VApal-treated eye and vehicle-treated eye (E). Abbreviation: VApal, vitamin A retinol palmitate.
Figure 2
Figure 2
Changes of the fluorescein score (A–C) and rose bengal score (D–F) treated with the VApal or vehicle. The fluorescein score and rose bengal score in VApal-treated eyes: Concentrations of VApal are 500 IU/mL (Δ) (A and D), 1000 IU/mL (⋄) (B and E) and 1500 IU/mL (○) (C and F) respectively. Notes: All data were compared to vehicle-treated eyes (■). Significant decreases of both fluorescein score and rose bengal score were shown in both 1000 IU/mL and 1500 IU/mL VApal-treated eyes compared to the vehicle-treated eyes after 7 days. *P < 0.05; **P < 0.01. All data are mean ± SE (n = 7). Abbreviations: VApal, vitamin A retinol palmitate; SE, standard error.
Figure 3
Figure 3
Light microscopic images showing the structure of the cornea stained with HE (A and B), and the lower tarsal conjunctiva stained with PAS (C and D). Corneal epithelium and conjunctival epithelium were recovered, goblet cells were increased at 7 days after treatment with 1500 IU/mL of VApal (B and D) compared with vehicle-treated eye (A and C). Note: Bars are 100 μm. Abbreviations: PAS, periodic acid–Schiff; VApal, vitamin A retinol palmitate.
Figure 4
Figure 4
Density of PAS positive cells in lower eyelid conjunctiva. Notes: Data were averaged from randomly selected three visual fields after treatments in vehicle-treated eyes (n = 21) and in VApal-treated eyes (n = 7 each). The VApal-treated eyes showed significantly greater numbers of density compared with the vehicle-treated eyes at 3 and 7 days. *P < 0.05; **P < 0.01. All data are mean ± SE. Abbreviations: PAS, periodic acid–Schiff; SE, standard error; VApal, vitamin A retinol palmitate.
Figure 5
Figure 5
Comparison of the effects with VApal and hyaluronic acid eye drops. The fluorescein score (A) and rose bengal score (B) in the 1500 IU/mL of VApal-treated eyes (○) showed significant decrease compared with the scores in the hyaluronic acid-treated eyes (▲) at 3 and 7 days. Notes: *P < 0.05; **P < 0.01. All data are mean ± SE (n = 7). Abbreviations: SE, standard error; VApal, vitamin A retinol palmitate.

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