Abstract
Purpose: To investigate the toxicity of the low-molecular-weight components (LMWCs) in ophthalmic silicone oils (SilOils) on retinal cell lines. Methods: The toxicity of six types of LMWCs were studied and compared with conventional SilOil 1000 cSt. In vitro cytotoxic tests of LMWCs, in both liquid and emulsified forms, on three retinal cell lines (Müller cells (rMC-1), photoreceptor cells (661W) and retinal pigment epithelial cells (ARPE-19)) were conducted using a transwell cell culturing system. The morphology and viability of cells were assessed by light microscopy and Cell Counting Kit-8 (CCK-8) assay at different time points (6, 24 and 72 h). The ARPE-19 apoptotic pathway was investigated by Mitochondrial Membrane Potential/Annexin V Apoptosis Kit at different time points (6, 24 and 72 h). Results: Apart from dodecamethylpentasiloxane (L5), all liquid LMWCs showed varying degrees of acute cytotoxicity on retinal cell lines within 72 h. Emulsified LMWCs showed comparable cytotoxicity with liquid LMWCs on retinal cell lines. Cyclic LMWCs, octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) had significantly higher cytotoxicity when compared with their linear counterparts decamethyltetrasiloxane (L4) and L5 with similar molecular formula. Using ARPE-19 cells as an example, we showed that LMWCs induce the apoptosis of retinal cells. Conclusions: Most LMWCs, in both liquid and emulsified forms, can induce acute cytotoxicity. In addition, cyclic LMWCs are suspected to have higher cytotoxicity than their linear counterparts. Therefore, LMWCs are suspected to be the main cause of the long-term toxicity of ophthalmic SilOil, due to their toxicity and propensity to cause ophthalmic SilOil to emulsify. The amount of LMWCs should be considered as the paramount parameter when referring to the quality of SilOil.
Highlights
Since the early years of vitrectomy surgery in the 1980s, SilOil became an important tool in the management of complicated vitreoretinal diseases
We showed the short-term cytotoxicity of low-molecular-weight components (LMWCs) in both liquid and emulsified forms on retinal cell lines in vitro
The molecular weight and molecular geometry may contribute to the difference in cytotoxicity between the various LMWCs tested
Summary
Since the early years of vitrectomy surgery in the 1980s, SilOil became an important tool in the management of complicated vitreoretinal diseases. LMWCs, considered as small molecule SilOils, are the building blocks of long-chain ophthalmic SilOil [9]. They are considered the main impurities in conventional ophthalmic SilOil because they are difficult to remove during the purification procedure. Their cytotoxicity has been proposed to be due to the diffusion of these small molecules into cells [10]. The emulsification of SilOil has been suggested to account for several postoperative complications, including secondary glaucoma and unexplained SilOil-related visual loss [13,14], as emulsified SilOil droplets were found in various ocular tissues [13,14,15,16]. The direct toxicity of LMWCs (both in liquid and emulsion form), as well as the chronic inflammation induced by the emulsification of long-chain SilOil due to LMWCs could be the potential mechanism of toxicity of SilOil at an intraocular setting
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