It was wonderful to go to ARVO this year and see how many poster and papers were about Stem Cell research. It is an exciting new field which I pray will lead to new options for my dry eye patients.
Here is a list of all the presentations on Stem Cell Research from 2016. 2017 is almost out.
This project used rats and showed Mesenchymal Stem Cells “activated proliferation of host cells and recruited immune cells to the microenvironment.” This could mean that a stem cell stimulates the cell where it is injected to make more of itself. In the meibomian gland this could be an indication that the stem cell might make the meibomian gands produce more of its glands: this is my hypothesis.
Program Number: 3896 Poster Board Number: A0044 Presentation Time: 3:45 PM–5:30 PM The fate of mesenchymal stem cells after subconjunctival implantation Juan Li, Chengyou Zuo, Shangkun Ou, Sanming Li, Liying Zhang, Changkai Jia, Zuguo Liu, Wei Li. Xiamen University Medical College, Eye Institute of Xiamen University, Xiamen, China. Purpose: Subconjunctival injection of mesenchymal stem cells (MSCs) has been applied in the treatment of ocular surface chemical burn, while the fate of MSCs in the local microenvironment after injection remains unknown. In this study, we investigated the survival, migration, proliferation, differentiation and paracrine of human MSCs, as well as their impact on the ocular surface microenvironment after subconjunctival implantation in rat. Methods: MSCs were isolated from umbilical cord characterized by flow cytometry on the basis of published criteria. Overall, 27 SD rats were subjected to MSCs injection. For each rat, the left eye was injected subconjunctivally with 2X105 MSCs suspended in 50ml DMEM, and the right eye was served as a control. On the 3rd, 6th and 9th day after injection, the rats were examined by slit-lamp to evaluate conjunctival edema and hyperemia. Immunohistochemistry was performed to investigate the expression patterns of Vimentin, a-SMA, Ki67 and PMN. TUNEL assay was performed to detect cell apoptosis. Furthermore, the proportion of CD11b+
Results: MSCs were isolated and their specific markers, such as CD29, CD44, CD105 and CD90, were expressed at high levels, while CD31, CD34, CD45 and MHC-DR could not be detected. Rat conjunctiva showed mild hyperemia at the injection site on the second day and diminished on day 3. All the injected cells remained in the engrafted regions and showed no migration. Majority of the MSCs survived 3 days after implantation. However, the number of cells gradually decreased thereafter, and completely disappeared on day 9 after implantation. Using Ki67 as a marker, we could only observe quite a number of positive staining cells surrounding the cell mass. Immunostaining against a-SMA was negative from day 3 to day 9, indicating that the injected cells did not differentiate into myofibroblasts. TUNEL positive cells were present in the injected cell mass. The quantities of infiltrated CD11b+, CD45+ and PMN+ cells were increased in the injected eyes at day 3, and gradually reduced to normal basal levels at day 9. Conclusions: MSCs were gradually eliminated from the injection site without cell migration, proliferation and differentiation. However, MSCs activated proliferation of host cells and recruited immune cells to the microenvironment. Commercial Relationships: Juan Li, None; Chengyou Zuo, None; Shangkun Ou, None; Sanming Li, None; Liying Zhang, None; Changkai Jia, None; Zuguo Liu, None; Wei Li, None Support: Chinese
This study had only a few patients but the photos of pre and post did look better.
Program Number: 3894 Poster Board Number: A0042 Presentation Time: 3:45 PM–5:30 PM Reproducibility and Outcomes of Simple Limbal Epithelial Transplantation (SLET) technique Alexandra Abdala, Arturo J. Ramirez-Miranda, Alejandro Lichtinger, Alejandro Navas, Enrique O. Graue-Hernandez. Instituto de Oftalmologia Conde de Valenciana, Mexico City, Mexico. Purpose: To report the results of simple limbal epithelial transplantation (SLET) for limbal stem cell deficiency (LSCD) at an ophthalmological institution in Mexico City. Methods: Five patients (5 eyes) with LSCD due to chemical injuries (3 eyes), thermal injury (1 eye) and failure of tectonic sclerokeratoplasty after corneal melting of tectonic patch graft secondary to rheumatoid arthritis perforation (1 eye). All patients had unilateral involvement and received an autologous graft of limbal stem cells from the contralateral healthy eye, technique described by Sangwan. Preoperative best-corrected visual acuity, postoperative best-corrected visual acuity, previous surgeries, side effects on the donor eye, time from injury to surgery, recurrence and postoperative complications were evaluated. Paired t test was used for statistical analysis. Results: Preoperative mean best-corrected visual acuity was 1.55LogMAR (1 to 2.3LogMAR). The mean follow-up was 10.2 months (6 to 14 months), with postoperative mean best-corrected visual acuity of 0.33LogMAR (0.17 to 0.47LogMAR). The ocular surface was improved in all patients, however focal recurrence with superficial corneal vascularization was observed on the affected eye. The donor eye did not have complications. Conclusions: The result of our study suggests that SLET is a safe and effective treatment option for the management of unilateral LSCD, improving the ocular surface for future corneal procedures.
This project: I have been doing Limbal Stem Cell Transplants since I was a resident at NYEE: class of 2000. We know these work for patients with chemical burns or significant limbal stem cell deficiency.
Program Number: 3894 Poster Board Number: A0042 Presentation Time: 3:45 PM–5:30 PM Reproducibility and Outcomes of Simple Limbal Epithelial Transplantation (SLET) technique Alexandra Abdala, Arturo J. Ramirez-Miranda, Alejandro Lichtinger, Alejandro Navas, Enrique O. Graue-Hernandez. Instituto de Oftalmologia Conde de Valenciana, Mexico City, Mexico. Purpose: To report the results of simple limbal epithelial transplantation (SLET) for limbal stem cell deficiency (LSCD) at an ophthalmological institution in Mexico City. Methods: Five patients (5 eyes) with LSCD due to chemical injuries (3 eyes), thermal injury (1 eye) and failure of tectonic sclerokeratoplasty after corneal melting of tectonic patch graft secondary to rheumatoid arthritis perforation (1 eye). All patients had unilateral involvement and received an autologous graft of limbal stem cells from the contralateral healthy eye, technique described by Sangwan. Preoperative best-corrected visual acuity, postoperative best-corrected visual acuity, previous surgeries, side effects on the donor eye, time from injury to surgery, recurrence and postoperative complications were evaluated. Paired t test was used for statistical analysis. Results: Preoperative mean best-corrected visual acuity was 1.55LogMAR (1 to 2.3LogMAR). The mean follow-up was 10.2 months (6 to 14 months), with postoperative mean best-corrected visual acuity of 0.33LogMAR (0.17 to 0.47LogMAR). The ocular surface was improved in all patients, however focal recurrence with superficial corneal vascularization was observed on the affected eye. The donor eye did not have complications. Conclusions: The result of our study suggests that SLET is a safe and effective treatment option for the management of unilateral LSCD, improving the ocular surface for future corneal procedures.
This project brings to light a new idea: finding the gene or medicines that would make stem cells resistant to toxins or stress. Cool!
Program Number: 3869 Poster Board Number: A0017 Presentation Time: 3:45 PM–5:30 PM Crosstalk Between Selective Autophagy and Nrf2-ARE Pathway Through p62/SQSTM1 Confers Limbal Stem Cell Resistance to Ultraviolet-A Irradiation Ying-Ting Chen1 , Maria Laggner1 , Florian Gruber2 , Erwin Tschachler2 , Ursula Schmidt-Erfurth1 , Andreas Pollreisz1 . 1 Department of Ophthalmology, Medical University of Vienna, Vienna, Austria; 2 Department of Dermatology, Medical University of Vienna, Vienna, Austria. Purpose: Recently we reported a cytoprotective role for autophagy and Nrf2-ARE pathway in physiological UVA-stressed limbal stem cells (LSC). The current study sought to identify the mechanistic underpinnings linking these two pathways. Methods: Krt14-Cre:Atg7f/f transgenic mice and global Nrf2-KO mice on C57BL/6 background were used to generate Atg7-/- and Nrf2- /- LSCs, respectively. 3-MA was used to inhibit autophagy in cultured Nrf2-/- LSCs for creating autophagy-deficient Nrf2-KO LSCs. UVA irradiation at a low dose (10 J/cm2 ) was applied to the cultured LSCs, pre-treated with either ROS-scanvenger NAC or drug vehicle. CMH2 DCFDA live staining and Caspase3/7 CytoEvent were used to detect intracellular ROS levels and cellular apoptosis, respectively. Autophagic activity was measured by CytoID live staining. Dual immunofluorescence was used to study the cellular kinetics of Nrf2 and p62/SQSTM1. A nuclear localization of Nrf2 was used as a surrogate readout for Nrf2-ARE activity. Results: Confocal microscopy using CM-H2 DCFDA live staining did not detect changes of ROS level in 10 J/Cm2-irradiated Atg7f/f LSCs. In contrast, a 2-3 fold elevation in ROS level was observed in Atg7-/-, Nrf2-/- and autophagy-deficient Nrf2-/- LSCs (all p<.05). Compared to the perspective non-irradiated baseline, Caspase3(+) apoptotic cells was increased by 3.5% (p>.05), 21.7% (p<.05), 29.3% (p<.05), and 18.4% (p<.05) in Atg7f/f, Atg7-/-, Nrf2-/- and autophagydeficient Nrf2-/-LSC at 24-hr post-irradiation. The radiation-induced apoptosis was successfully rescued by NAC pre-treatment. Dual immunofluorescence revealed a diffuse cytosolic distribution for Nrf2 and p62 in unstressed LSCs, with a low-degree co-localization. After irradiation, Nrf2 nuclear translocation was observed exclusively in Atg7f/f cells with distinct p62 perinuclear speckle formation. Such a Nrf2/p62 redistribution was not seen in any other irradiated groups. Conclusions: Our data collectively suggest that autophagy activation in LSCs under physiological UVA stress functions as a non-canonical antioxidant defense mechanism. The p62/SQSTM1-mediated enhancement of Nrf2-ARE response enables LSC to have a tighter control in cellular redox. New therapeutics targeting p62/SQSTM1 might thus supplement the current antioxidant-based treatment for corneal degenerative diseases associated chronic oxidative stress.