Effect of Penetrating Keratoplasty and Keratoprosthesis Implantation on the Posterior Segment of the Eye

Purpose To compare the effects of post-penetrating keratoplasty (PK) and post-keratoprosthesis (KPro) surgery-related inflammation on the posterior segment of the eye and to assess inhibition of tumor necrosis factor alpha (TNFα) and interleukin-1 beta (IL-1β) on these effects. Methods: BALB/C (syngeneic) or C57BL/6 (allogeneic) corneas were transplanted onto BALB/C host beds as part of PK or miniature KPro (m-KPro) implantation. Intraocular pressure (IOP) was measured via an intracameral pressure sensor; tissues were harvested and analyzed 8 weeks after surgery. Expression of TNFα and IL-1β in the retina was analyzed using real-time quantitative (q)PCR. Optic nerve degeneration (axon count, circularity, and area) was assessed quantitatively using ImageJ software. After m-KPro implantation, mice were treated with saline, anti-TNFα, or anti-IL-1β antibody, and axonal loss was assessed after 10 weeks. Results: Mean IOP was within normal limits in the operated and fellow eyes in all groups. The mRNA expression of TNFα and IL-1β was highest in m-KPro groups with either syngeneic or an allogeneic carrier. We observed optic nerve degeneration in both allogeneic PK and m-KPro implanted eyes with an allogeneic carrier. However, TNFα blockade significantly reduced axonal loss by 35%. Conclusions: Allogeneic PK and m-KPro implants with an allogeneic carrier lead to chronic inflammation in the posterior segment of the eye, resulting in optic nerve degeneration. In addition, blockade of TNFα prevents axonal degeneration in this preclinical model of allogeneic m-KPro (alloKPro) implantation

Effect of Penetrating Keratoplasty and Keratoprosthesis Implantation on the Posterior Segment of the Eye

Citation:Črnej A, Omoto M, Dohlman TH, et al. Effect of penetrating keratoplasty and keratoprosthesis implantation on the posterior segment of the eye. Invest Ophthalmol Vis Sci. 2016;57:164357: -164857: . DOI:10.1167 PURPOSE. To compare the effects of post-penetrating keratoplasty (PK) and post-keratoprosthesis (KPro) surgery-related inflammation on the posterior segment of the eye and to assess inhibition of tumor necrosis factor alpha (TNFa) and interleukin-1 beta (IL-1b) on these effects. METHODS. BALB/C (syngeneic) or C57BL/6 (allogeneic) corneas were transplanted onto BALB/ C host beds as part of PK or miniature KPro (m-KPro) implantation. Intraocular pressure (IOP) was measured via an intracameral pressure sensor; tissues were harvested and analyzed 8 weeks after surgery. Expression of TNFa and IL-1b in the retina was analyzed using real-time quantitative (q)PCR. Optic nerve degeneration (axon count, circularity, and area) was assessed quantitatively using ImageJ software. After m-KPro implantation, mice were treated with saline, anti-TNFa, or anti-IL-1b antibody, and axonal loss was assessed after 10 weeks. RESULTS. Mean IOP was within normal limits in the operated and fellow eyes in all groups. The mRNA expression of TNFa and IL-1b was highest in m-KPro groups with either syngeneic or an allogeneic carrier. We observed optic nerve degeneration in both allogeneic PK and mKPro implanted eyes with an allogeneic carrier. However, TNFa blockade significantly reduced axonal loss by 35%. CONCLUSIONS. Allogeneic PK and m-KPro implants with an allogeneic carrier lead to chronic inflammation in the posterior segment of the eye, resulting in optic nerve degeneration. In addition, blockade of TNFa prevents axonal degeneration in this preclinical model of allogeneic m-KPro (alloKPro) implantation

Induced Pluripotent Stem Cells: Development in the Ophthalmologic Field

Human induced pluripotent stem cells (iPSCs) are a type of stem cells that can be derived from human somatic cells by introducing certain transcription factors. Induced pluripotent stem cells can divide indefinitely and are able to differentiate into every cell type, which make them viable for transplantation and individual disease modeling. Recently, various ocular cells, including corneal epithelial-like cells, retinal pigment epithelium (RPE) cells displaying functions similar to native RPE, photoreceptors, and retinal ganglion cells, have all been successfully derived from iPSCs. Transplantation of these cells in animal models showed great promise for reversing blindness, and the first clinical trial on humans started in 2013. Despite these promising results, more research is in demand for preventing inadvertent tumor growth, developing precise functionality of the cells, and promoting integration into the host tissue