## 4 Discussion  
This study investigated the role of Myo/Nog cells in the context of retinal degeneration, emphasizing their phagocytic activity and potential neuroprotective contributions in the C3H/HeI mouse model of retinitis pigmentosa (RP). The findings align with and expand upon existing research, underscoring the multifaceted roles of Myo/Nog cells in response to tissue stress and degeneration. Figure 7: **Myo/Nog cells phagocytose apoptotic photoreceptors in C3H retinas. Tissue section of a C3H retina labeled with TUNEL reagents (red) (B,C,E,F), anti-BAI1 mAb (green) (A,C,D,F), and DAPI for nuclei (blue) (A–F). Arrows indicate BAI1+ Myo/Nog cells in the ONL phagocytosing apoptotic cellular debris. **  
The increased presence of Myo/Nog cells in the ONL and choroid of C3H/HeJ mice observed in this study complements earlier reports of their migration to injury sites in both ocular and non-ocular tissues. Prior work has established that Myo/Nog cells rapidly respond to acute stress, such as light-induced damage [16] and glaucomatous injury [6]. This study extends these observations to a chronic model of degeneration, showing that Myo/Nog cells dynamically engage in apoptotic debris clearance, a process critical for maintaining retinal homeostasis. In previous studies, we have shown that Myo/Nog cells, under certain conditions, work as non-professional phagocytes [15]. Non-professional phagocytes are cells whose main role is not immune defense, but which can still phagocytose under certain conditions [14; 17; 18; 19]. This role is consistent with the capacity of Myo/Nog cells to express BAII, a mediator of apoptotic cell phagocytosis [14]. In addition to Myo/Nog cells functioning as non-professional phagocytes, these cells also express BAII, which is known to be a mediator in phagocytosis [14; 20]. It is believed that BAII's role in phagocytosis is through its interaction with the lipid phosphatidylserine (PtdSer), which signals the phagocytosis of apoptotic cells [14]. After BAII directly binds to PtdSer, BAII interacts with the ELMO/Dock180/Rac proteins, leading to actin cytoskeleton rearrangement and thus allowing for the uptake of apoptotic cells [14; 21]. The phagocytic behavior of the BAII-expressing Myo/Nog cells is likely triggered by this mechanism through phosphatidylserine (PtdSer), which accumulates on the outer leaflet of apoptotic photoreceptor membranes. Oxidative stress and damage-associated molecular patterns (DAMPs) such as HMGB1 may further augment this activity, as observed in other phagocytic contexts [22; 23; 24]. While our study focused on BAII as a marker of Myo/Nog cells, additional phagocytic markers, such as METK, TIM-4, or Gas6, have not yet been characterized in this cell type. Future investigations should assess whether Myo/Nog cells express these or other phagocytic regulators in the context of retinal degeneration. In the retina, microglia are traditionally considered the primary immune cells responsible for debris clearance [25; 26]. However, our findings suggest that Myo/Nog cells provide complementary support to microglia in the stressed ONL of degenerating retinas. This dual engagement of phagocytic cells may enhance the efficiency of apoptotic cell clearance and reduce the risk of chronic inflammation, which is a known contributor to secondary retinal damage [27]. The combined effect of Myo/Nog cells acting as non-professional phagocytes and BAII being a mediator in phagocytosis aligns well with their proposed function in neuroprotection, as the phagocytosis of this debris may protect the retina from further damage. Recent research has emphasized the complex interplay between microglia and other support cells in shaping inflammatory responses during retinal degeneration. The transcriptomic profiling of degenerating retinas has identified distinct shifts in phagocytic gene expression across multiple cell types, including Muller glia and astrocytes, which may work in tandem with or independently of microglia [25; 26].