Keratoconjunctivitis Sicca and Conjunctival Antigen-Presenting Cells

• Applicant: Dr. Aytan Musayeva
• Subject Area: Ophthalmology
• Term: from 2019 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 432369380

• Final Report Year: 2025

Final Report Abstract

Corneal transplantation is the most common form of solid tissue grafting, with approximately 85–90% success rates. However, the success rates significantly decline when donor tissues are derived from patients with a history of diabetes mellitus (DM). To evaluate the underlying immunopathological processes that cause graft rejection, we used streptozotocin-induced diabetic murine models as donors and non-diabetic BALB/c as recipients. DM led to increased frequency of corneal antigen-presenting cell (APC) with an acquired immunostimulatory phenotype. Following transplantation, recipients who received diabetic grafts showed increased APC migration, impaired functional regulatory T-cells (Treg) and graft survival. We conclude DM impact corneal APC functional phenotype which is a risk factor for diabetic graft failure. Future work will further explore the mechanisms of DM-related graft rejection and their treatment mechanisms.

Publications

• A Novel Murine Model of Endothelial Keratoplasty. Cornea, 42(2), 224-231.
  Nakagawa, Hayate; Blanco, Tomas; Kahale, Francesca; Wang, Shudan; Musayeva, Aytan; Alemi, Hamid; Dohlman, Thomas H. & Dana, Reza
  
• Amplified Natural Killer Cell Activity and Attenuated Regulatory T-cell Function Are Determinants for Corneal Alloimmunity in Very Young Mice. Transplantation, 107(6), 1302-1310.
  Nakao, Takeshi; Inomata, Takenori; Blanco, Tomas; Musayeva, Aytan; Tahvildari, Maryam; Amouzegar, Afsaneh; Yin, Jia; Chauhan, Sunil K.; Chen, Yihe & Dana, Reza
  
• Modulating the tachykinin: Role of substance P and neurokinin receptor expression in ocular surface disorders. The Ocular Surface, 25, 142-153.
  Singh, Rohan Bir; Naderi, Amirreza; Cho, Wonkyung; Ortiz, Gustavo; Musayeva, Aytan; Dohlman, Thomas H.; Chen, Yihe; Ferrari, Giulio & Dana, Reza
  
• Ocular pain in ocular graft-versus-host disease patients with neurotrophic keratopathy. The Ocular Surface, 26, 142-147.
  Wang, Shudan; Singh, Rohan Bir; Yuksel, Erdem; Musayeva, Aytan; Sinha, Shruti; Taketani, Yukako; Dohlman, Thomas H. & Dana, Reza
  
• Promotion of corneal angiogenesis by sensory neuron-derived calcitonin gene-related peptide. Experimental Eye Research, 220, 109125.
  Zhu, Shuyan; Zidan, Asmaa; Pang, Kunpeng; Musayeva, Aytan; Kang, Qianyan & Yin, Jia
  
• Insights into mustard gas keratopathy- characterizing corneal layer-specific changes in mice exposed to nitrogen mustard. Experimental Eye Research, 236, 109657.
  Alemi, Hamid; Dehghani, Shima; Forouzanfar, Katayoon; Surico, Pier Luigi; Narimatsu, Akitomo; Musayeva, Aytan; Sharifi, Sina; Wang, Shudan; Dohlman, Thomas H.; Yin, Jia; Chen, Yihe & Dana, Reza
  
• The impact of donor diabetes on corneal transplant immunity. American Journal of Transplantation, 23(9), 1345-1358.
  Blanco, Tomás; Musayeva, Aytan; Singh, Rohan Bir; Nakagawa, Hayate; Lee, Seokjoo; Alemi, Hamid; Gonzalez-Nolasco, Bruno; Ortiz, Gustavo; Wang, Shudan; Kahale, Francesca; Dohlman, Thomas H.; Chen, Yihe & Dana, Reza
  
• Acquired immunostimulatory phenotype of migratory CD103+ DCs promotes alloimmunity following corneal transplantation. JCI Insight, 9(20).
  Blanco, Tomás; Nakagawa, Hayate; Musayeva, Aytan; Krauthammer, Mark; Singh, Rohan Bir; Narimatsu, Akitomo; Ge, Hongyan; Shoushtari, Sara I. & Dana, Reza
  
• Assessment of Corneal Graft Outcomes in a Murine Model of Endothelial Keratoplasty. Journal of Clinical Medicine, 13(17), 5010.
  Narimatsu, Akitomo; Singh, Rohan Bir; Surico, Pier Luigi; Lee, Seokjoo; Forouzanfar, Katayoon; Kahale, Francesca; Musayeva, Aytan; Dohlman, Thomas H.; Blanco, Tomas & Dana, Reza
  
• Myeloid-derived suppressor cells promote allograft survival by suppressing regulatory T cell dysfunction in high-risk corneal transplantation. American Journal of Transplantation, 24(9), 1597-1609.
  Lee, Seokjoo; Blanco, Tomas; Musayeva, Aytan; Dehghani, Shima; Narimatsu, Akitomo; Forouzanfar, Katayoon; Ortiz, Gustavo; Kahale, Francesca; Wang, Shudan; Chen, Yihe; Dohlman, Thomas H.; Chauhan, Sunil K. & Dana, Reza
  
• The Neuropeptide α-Melanocyte–Stimulating Hormone Prevents Persistent Corneal Edema following Injury. The American Journal of Pathology, 194(1), 150-164.
  Alemi, Hamid; Wang, Shudan; Blanco, Tomas; Kahale, Francesca; Singh, Rohan B.; Ortiz, Gustavo; Musayeva, Aytan; Yuksel, Erdem; Pang, Kunpeng; Deshpande, Neha; Dohlman, Thomas H.; Jurkunas, Ula V.; Yin, Jia & Dana, Reza
  
• Antagonizing NK-1R modulates pain perception following corneal injury. Experimental Eye Research, 251, 110230.
  Surico, Pier Luigi; Naderi, Amirreza; Singh, Rohan Bir; Kahale, Francesca; Farsi, Yeganeh; Lee, Seokjoo; Musayeva, Aytan; Chen, Yihe & Dana, Reza