Dataset Information

Dual-function thermogelling polymers as effective endotamponade for retinal detachment repair and reassembly of vitreous-like body in-situ

ABSTRACT: Endo-tamponade agents are crucial surgical adjuncts for vitreo-retinal surgery. Current clinical agents provide internal tamponade through buoyancy forces requiring the need for prolonged facing down post-operative positioning. Other disadvantages include temporary loss of vision, raised intra-ocular pressure, cataract formation and a need for an additional removal surgery. Therein lies an unmet clinical need to develop alternative biomaterials to overcome these key challenges. We describe a biocompatible and biodegradable thermogelling polymer which provides an internal tamponade effect through surface tension and viscosity. Furthermore, we demonstrate its surgical efficacy in the repair of retinal detachment in a non-human primate model. By three-month post-surgery, the thermogel undergoes biodegradation, and is replaced by a vitreous-like body, thereby mimicking the biophysical needs of the natural vitreous body. In summary, we demonstrate the potential superiority of our thermogel compared to current vitreous tamponade gold standards; and present a significant advancement in the use of biomaterials for vitreo-retinal surgery.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Oryctolagus Cuniculus (rabbit)

TISSUE(S): Vitreous Humor

DISEASE(S): Retinal Detachment

SUBMITTER: Asfa Alli Shaik

LAB HEAD: Jayantha GUNARATNE

PROVIDER: PXD009525 | Pride | 2019-09-13

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	TBP_F_P4_180118_05_IS1068_p48OD.raw	Raw
	TBP_F_P4_180118_11_IS1068_p51OD.raw	Raw
	TBP_F_P4_180118_17_IS1068_p52OD.raw	Raw
	TBP_F_P4_180118_23_IS1068_p47OD.raw	Raw
	TBP_F_P4_180118_29_IS1068_p49OD.raw	Raw

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Publications

Retinal-detachment repair and vitreous-like-body reformation via a thermogelling polymer endotamponade.

Liu Zengping Z Liow Sing Shy SS Lai Siew Li SL Alli-Shaik Asfa A Holder Graham E GE Parikh Bhav Harshad BH Krishnakumar Subramanian S Li Zibiao Z Tan Mein Jin MJ Gunaratne Jayantha J Barathi Veluchamy Amutha VA Hunziker Walter W Lakshminarayanan Rajamani R Tan Clement Woon Teck CWT Chee Caroline K CK Zhao Paul P Lingam Gopal G Loh Xian Jun XJ Su Xinyi X

Nature biomedical engineering 20190408 8

Internal-tamponade agents are crucial surgical adjuncts in vitreoretinal surgery. Clinically used endotamponade agents act through buoyancy forces, yet can result in prolonged post-operative positioning, temporary loss of vision, raised intra-ocular pressure, cataract formation or the need for additional removal surgery. Here, we describe a thermogelling polymer that provides an internal tamponade effect through surface tension and swelling counter-forces. We tested the long-term biocompatibilit ...[more]

PMID: 30962587

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Project description:Reduced oxygenation of photoreceptors and the RPE in the ageing eye may be a risk factor for the development of both neovascular and dry AMD. Chronic activation of the molecular response to hypoxia in RPE or photoreceptors leads to retinal degeneration that depends on hypoxia inducible transcription factors. For approaching the identification of accessible markers characteristic for photoreceptors with an activated hypoxic response, we used a proteomics approach to determine the protein composition of the vitreous humor in mice. To discriminate between rod and cone-specific effects we used genetically modified mice that had the hypoxic response activated specifically in rods of a rod-dominant retina (rodΔVhl) or a genetically engineered all-cone retina (coneΔVhl). For comparison, we used wild-type mice exposed for 6 hours to acute hypoxia. We identified 1,357 unique proteins in the vitreous of mice after acute hypoxia, 1,624 in rodΔVhl and 1,895 in coneΔVhl mice. Of these, 1,043 proteins were common to all three types of mice. Of the identified proteins, 257 were significantly regulated by a factor of 1.5 or more in hypoxic mice, 258 in rodΔVhl and 356 in coneΔVhl mice in at least one of the three analyzed time points. Only 51 of the significantly regulated proteins were common to the vitreous of rodΔVhl and coneΔVhl mice, suggesting different consequences of the activated hypoxic response for rods and cones. Guanylate binding protein 2 (GBP2) was found at increased levels in the vitreous of both rodΔVhl and coneΔVhl mice at all time points tested. This was also reflected by increased gene expression in the retina. Although retinal expression of the AMD-associated gene alpha-2 macroglobulin (A2M) appeared increased in both types of mice, the protein was only found elevated in the vitreous of rodΔVhl mice. Other proteins found increased included Serpina3n, synaptosome associated protein 25 (SNAP25) and others. The distinct protein compositions present at early and late time points, suggest a well-regulated process in our models. We hypothesize that some of the proteins identified at early time points may potentially be used as markers for the chronic hypoxic response of photoreceptors.