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As graphene becomes one of the most exciting candidates for multifunctional biomedical applications, contact between eyes and graphene-based materials is inevitable. On the other hand, eyes, as a special organ in the human body, have unique advantages to be used for testing new biomedical research and development, such as drug delivery. Intraocular biocompatible studies on graphene-related materials are thus essential. Here, we report our recent studies on intraocular biocompatibility and cytotoxicity of graphene oxide (GO) both in vitro and in vivo. The successful preparation of GO nanosheets was confirmed using atomic force microscopy, contact angle analyzer, Fourier transform infrared spectroscopy, and Raman spectroscopy. The influence of GO on human retinal pigment epithelium (RPE) cells in terms of the cell morphology, viability, membrane integrity, and apoptosis was investigated using various techniques, including optical micrography, cell counting kit-8 (CCK-8) assay, lactate dehydrogenase (LDH) assay, and apoptosis assay. The addition of GO had little influence on cell morphology, but the change was visible after long-time culturing. RPE cells showed higher than 60% cell viability by CCK-8 assay in GO solutions and less than 8% LDH release, although a small amount of apoptosis (1.5%) was observed. In vitro results suggested good biocompatibility of GO to RPE cells with slight adverse influence, on the cell viability and morphology in long-time periods, along with aggregation of GO. Thus, some further studies are needed to clarify the cytotoxicity mechanism of GO. GO intravitreally injected eyes showed few changes in eyeball appearance, intraocular pressure (IOP), eyesight, and histological photos. Our results suggested that GO did not cause any significant toxicity to the cell growth and proliferation. Intravitreal injection of GO into rabbits' eyes did not lead to much change in the eyeball appearance, IOP, electroretinogram, and histological examination.

The noninvasive and real-time detection of glucose sugar from tears is promising for the early diagnosis and treatment of chronic diseases such as diabetes. However, its realization is a big challenge. A suitable biosensor electrode that can closely fit the eye and be electrochemically sensitive is still unrealized. In this work, nitrogen-doped graphene (N-G) was used as an ophthalmic electrode in a high-performance intraocular biosensor. The use of N-G has been reported elsewhere before as it is highly electroactive and so has a particular use in biosensors. We hereby present a novel procedure for making carboxylated chitosan-functionalized nitrogen-containing graphene (GC–COOH) by using a one-step ball-milling process. This process does not use toxic chemicals, flammable gases, or a high temperature. It is thus particularly easy to perform. The fabricated nanomaterial had a high electroactivity and was easily assembled as a glucose biosensor by the immobilization of glucose oxidase. The thus constructed biosensor has a high sensitivity at 9.7 μA mM–1 cm–2, a broad linear range at 12 mM, and a good detection limit of 9.5 μM. It was able to maintain this activity after a month of storage. We also report the intraocular use of this constructed biosensor. The as-prepared GC–COOH was found to be highly biocompatible to ophthalmologic cells such as corneal epithelial and retinal pigment epithelium cells. No change in the intraocular pressure or the corneal structure was measured in a New Zealand white rabbit model. The as-assembled sensor was worn by the animals for more than 24 h without undue impact. This result confirmed the biosensor’s potential for intraocular application in the clinic. Its assembly into a useful sensor shown here has great potential to provide real-time monitoring of glucose levels in tear fluids of patients with high sugar levels.

Inactivation of GPR48 induces the EOB phenotype by reducing epithelial cell proliferation and migration, indicating that GPR48 plays an essential role in eyelid development. Furthermore, GPR48 contributes to eyelid development through the regulation of the EGFR signaling pathway.

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