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Immunohistochemical Characterization of Intraocular Inflammation After Intravitreal Administration of Biologics to
Theresa C Brömel1, Barbara Lenz1, Rachel Neff1
1F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Intraocular inflammation (IOI) following intravitreal (IVT) administration of large molecules (LM) is commonly seen in preclinical species and often relates to the presence of systemic anti-drug antibodies (ADA) as a reaction to the application of human proteins into a non-human species. This retrospective study aimed to characterize histopathological findings of IOI after IVT administration of LMs to non-human primates (NHP) and minipigs. Three independent safety studies were analyzed using immunohistochemical and special stains for inflammatory cell markers (CD68, Iba1, CD163, CD3, CD20, CD138), glial cell markers (glial fibrillary acidic protein [GFAP], vimentin, glutamine synthetase [GS]), and extracellular matrix (ECM) (fibronectin, collagen I, trichrome staining). Mononuclear cell infiltrates, membrane formation, and retinal degeneration were assessed. Infiltrates in various ocular compartments consisted mainly of monocytes/macrophages, T cells, and plasma cells, indicating an ongoing adaptive immune response. Membranes were primarily composed of glial cells (GFAP, vimentin positive) with a lack of substantial ECM deposition. Retinal degeneration correlated with increased GFAP/vimentin and decreased GS staining in the retina. Overall, these results correlated with the presence, location, and severity of the histopathologic diagnoses and were consistent between the two species. This study provides a detailed characterization of IOI consistent with an adaptive immune response following IVT administration of LM, enhancing our understanding of the ongoing immunological processes.
Intraocular inflammation (IOI) following intravitreal (IVT) administration of large molecules (LM) is commonly seen in preclinical species and often relates to the presence of systemic anti-drug antibodies (ADA) as a reaction to the application of human proteins into a non-human species. This retrospective study aimed to characterize histopathological findings of IOI after IVT administration of LMs to non-human primates (NHP) and minipigs. Three independent safety studies were analyzed using immunohistochemical and special stains for inflammatory cell markers (CD68, Iba1, CD163, CD3, CD20, CD138), glial cell markers (glial fibrillary acidic protein [GFAP], vimentin, glutamine synthetase [GS]), and extracellular matrix (ECM) (fibronectin, collagen I, trichrome staining). Mononuclear cell infiltrates, membrane formation, and retinal degeneration were assessed. Infiltrates in various ocular compartments consisted mainly of monocytes/macrophages, T cells, and plasma cells, indicating an ongoing adaptive immune response. Membranes were primarily composed of glial cells (GFAP, vimentin positive) with a lack of substantial ECM deposition. Retinal degeneration correlated with increased GFAP/vimentin and decreased GS staining in the retina. Overall, these results correlated with the presence, location, and severity of the histopathologic diagnoses and were consistent between the two species. This study provides a detailed characterization of IOI consistent with an adaptive immune response following IVT administration of LM, enhancing our understanding of the ongoing immunological processes.
