Compositions and methods for visualization of the vitreous
The invention provides compositions for rendering a vitreous cavity visible during a surgical procedure to alleviate a structural disorder caused by the vitreous in an eye, and methods of using the compositions. The compositions are vitreous delineating agents that comprise a hyaluronan binding peptide linked to an optically detectable moiety. Such compositions can be in a formulation that may be a solution, a suspension, or an emulsion, and would be injected into the vitreous shortly prior to use. The composition may additionally contain a therapeutic agent, a diagnostic agent, or a chemosensing material, in use, the composition marks or delineates the vitreous by binding preferentially to the hyaluronan that permeates the vitreous humor and binding little or not at all to surrounding tissues such as the retina. The interface between the labelled vitreous humor and the non-labelled surrounding vital tissues produces a visible signal, thereby allowing a surgeon to clearly visualize the entire vitreous cavity and distinguish it from vital ocular structures. Use of the method improves the accuracy and safety of a vitrectomy and thus prevents suboptimal outcomes or the need for repeated procedures. The compositions comprising chemosensing material are useful as long-lasting biosensors, which when used in the vitreous enable repetitive, non-invasive, in vivo measurements of metabolites or pharmacologic agents in the vitreous of animals or humans.
1. A method of visualizing the vitreous during vitrectomy surgery comprising:
injecting into an eye an inert composition comprising a peptide that binds hyaluronan that is linked to an optically detectable moiety in an amount effective to render the vitreous visible, wherein (i) the peptide comprises a sequence selected from the group consisting of: SEQ ID NO: 6 and 95 consecutive amino acids of the sequence of SEQ ID NO: 6, and (ii) the peptide is linked to fluorescein isothiocyanate.
2. The method of claim 1 , wherein said composition is formulated as a vesicle selected from the group consisting of a liposome and a microsphere.
3. The method of claim 1 , wherein said composition has a formulation selected from the group consisting of a solution, an emulsion, and a suspension.
4. A method of staining the vitreous in a mammalian eye comprising:
injecting a composition comprising a peptide linked to fluorescein isothiocyanate wherein the peptide comprises a sequence selected from the group consisting of SEQ ID NO: 6 and 95 consecutive amino acids of SEQ ID NO: 6 into the mammalian eye; and
applying an energy source selected from a light or laser to the eye to generate a signal from the fluorescein isothiocyanate.