The finding that subretinal bleb formation by isotonic saline solutions caused damage to the outer retinal layers and RPE is in overall accordance with previous in vivo studies. In a short-term ultrastructural study, subretinal injection of BSS in rabbits was shown to cause fragmentation of photoreceptor outer segments and disruption of the RPE within 3 minutes after injection.
20 In cynomolgus macaque, a similar treatment led to milder ultrastructural changes in the photoreceptor/RPE interphase that persisted for up to 3 months.
19 In a recent retrospective study in patients operated for retinal detachment, it was found that the outer retinal becomes significantly thinner after successful surgery and that the time until surgery is correlated with the extent of the degeneration.
24 Compared to these results, the changes observed in our study were apparently much more pronounced and long-lasting and included significant loss of the photoreceptor layer. The force of the retinal–RPE adhesion has been well characterized and is known to be higher in primates than in rabbits.
25 Indeed, the rabbit retina possesses several unique anatomic features not present in the humans or nonhuman primates.
26 The retinal vessels are merangiotic, and the myelinated nerve fibers radiate horizontally from the optic nerve forming the medullary ray. In addition, the macula is replaced by a horizontal visual streak below the optic nerve head. These differences may potentially affect retinal adhesiveness in the rabbit. Furthermore, adhesiveness is influenced by metabolic factors, and pretreatment of the vitreous cavity with low Ca
2+ and Mg
2+ solutions reduces retinal adhesion.
20,27 In the present study, we performed subretinal injections without prior vitrectomy or vitreous pretreatment and used standard PBS or BSS solutions. It is likely that together these factors contributed to maintain a strong retinal adhesion that in turn lead to the damage observed after bleb induction. At the molecular level, retinal adhesion is complex and not fully understood. It presumably involves apical surface receptors on the RPE and ligands in the interphotoreceptor matrix.
28 Recently, α
vβ
5 integrin, exclusively located on the apical part of the RPE, was the first receptor to be implicated as demonstrated in mice lacking α
vβ
5 integrin showing reduced RPE–photoreceptor OS adherence.
29 The pronounced loss of photoreceptors demonstrated by our data suggests that acute disruption of such receptor–ligand interactions may not be recovered, thus potentially leading to irreversible damage.