Autoimmune uveitis (AU) is a sight-threatening inflammatory disorder characterized by dysregulated immune responses in the retina, yet the molecular mechanisms governing macrophage-driven pathology remain incompletely understood. Here, we identify Leucine-Rich Pentatricopeptide Repeat Containing Protein (LRPPRC) as a critical regulator of macrophage inflammatory function and demonstrate that its downregulation contributes to the pathogenesis of AU. Analysis of the GSE209567 dataset revealed significant downregulation of LRPPRC in the bulk retinal tissues of AU patients compared to healthy controls, a finding recapitulated in Lipopolysaccharide (LPS) -stimulated macrophages in vitro. Functional studies in RAW264.7 cells demonstrated that siRNA-mediated LRPPRC knockdown promoted M1 polarization with increased iNOS, TNF-α, and IL-12 expression, while suppressing M2-associated markers. Conversely, LRPPRC overexpression attenuated LPS-induced inflammatory gene expression through inhibition of the NF-κB pathway, while paradoxically enhancing redox homeostasis with reduced ROS and preserved NAD+ levels. To investigate the in vivo relevance of these findings, we generated myeloid-specific LRPPRC knockout (LRPPRCLKO) mice and subjected them to Experimental Autoimmune Uveitis (EAU). LRPPRCLKO mice developed significantly more severe ocular pathology, characterized by exacerbated clinical scores, diffuse pan-retinal leukocyte infiltration, and profound disruption of the blood-retinal barrier. Flow cytometric analysis revealed enhanced retinal infiltration of neutrophils and macrophages, with infiltrating macrophages exhibiting a pro-inflammatory polarization signature and elevated IL-1β/IL-6 production. Notably, LRPPRC deficiency induced systemic immune dysregulation, with splenic expansion of neutrophils, macrophages, Thymus-derived helper T cell type 1 (Th1) cells, and Thymus-derived helper T cell type 17 (Th17) cells, accompanied by reduced regulatory T cells. Mechanistically, retinal tissues from LRPPRCLKO mice displayed concurrent activation of NF-κB signaling and oxidative stress responses. These findings establish LRPPRC as a key molecular integrator linking macrophage polarization, NF-κB signaling, and redox homeostasis, with its deficiency in myeloid cells creating a permissive environment for uncontrolled neuroinflammation. Our study identifies LRPPRC as a potential therapeutic target for autoimmune uveitis and related inflammatory disorders. Zusammenfassung Autoimmune Uveitis (AU) ist eine sehbedrohende entzündliche Erkrankung, die durch fehlregulierte Immunantworten in der Netzhaut gekennzeichnet ist, doch die molekularen Mechanismen, die der Makrophagen-gesteuerten Pathologie zugrunde liegen, sind nach wie vor unvollständig verstanden. Hier identifizieren wir das Leucin-reiche Pentatricopeptid-Wiederholungen enthaltende Protein (LRPPRC) als einen kritischen Regulator der entzündlichen Funktion von Makrophagen und zeigen, dass seine Herunterregulierung zur Pathogenese der AU beiträgt. Die Analyse des Datensatzes GSE209567 ergab eine signifikante Herunterregulierung von LRPPRC in den Netzhäuten von AU-Patienten im Vergleich zu gesunden Kontrollen, ein Befund, der in vitro in Lipopolysaccharid (LPS)-stimulierten Makrophagen reproduziert wurde. Funktionelle Studien in RAW264.7-Zellen zeigten, dass siRNA-vermittelter LRPPRC-Knockdown die M1-Polarisierung mit erhöhter iNOS-, TNF-α- und IL-12-Expression förderte, während gleichzeitig M2-assoziierte Marker unterdrückt wurden. Umgekehrt schwächte die LRPPRC-Überexpression die LPS-induzierte Entzündungsgenexpression durch Hemmung des NF-κB-Signalwegs ab, während sie paradoxerweise die Redox-Homöostase durch reduzierte ROS und erhaltene NAD⁺-Spiegel verbesserte. Um die In-vivo-Relevanz dieser Befunde zu untersuchen, generierten wir myeloizellspezifische LRPPRC-Knockout-Mäuse (LRPPRC^LKO) und unterzogen sie der experimentellen autoimmunen Uveitis (EAU). LRPPRC^LKO-Mäuse entwickelten eine signifikant schwerere okuläre Pathologie, gekennzeichnet durch verschlechterte klinische Scores, diffuse panretinale Leukozyteninfiltration und eine tiefgreifende Störung der Blut-Retina-Schranke. Die durchflusszytometrische Analyse zeigte eine verstärkte Netzhautinfiltration von Neutrophilen und Makrophagen, wobei die infiltrierenden Makrophagen ein proinflammatorisches Polarisierungssignatur und eine erhöhte IL-1β/IL-6-Produktion aufwiesen. Bemerkenswerterweise induzierte der LRPPRC-Mangel eine systemische Immundysregulation mit Milzvergrößerung von Neutrophilen, Makrophagen, Thymus-abgeleiteten Helfer-T-Zellen vom Typ 1 (Th1) und Thymus-abgeleiteten Helfer-T-Zellen vom Typ 17 (Th17), begleitet von reduzierten regulatorischen T-Zellen. Mechanistisch betrachtet zeigten Netzhautgewebe von LRPPRC^LKO-Mäusen eine gleichzeitige Aktivierung des NF-κB-Signalwegs und von oxidativen Stressreaktionen. Diese Ergebnisse etablieren LRPPRC als einen zentralen molekularen Integrator, der Makrophagenpolarisierung, NF-κB-Signalgebung und Redox-Homöostase verknüpft, wobei sein Mangel in myeloischen Zellen ein permissives Umfeld für unkontrollierte Neuroinflammation schafft. Unsere Studie identifiziert LRPPRC als potenzielles therapeutisches Ziel für autoimmune Uveitis und verwandte entzündliche Erkrankungen.
Background Patients undergoing intraocular lens (IOL) implantation typically have high expectations for the optical outcome. Accurate IOL positioning and stability are crucial, and various methods exist for assessing these factors. This study aims to investigate how the Carlevale IOL, available for aphakia correction in cases of capsular bag instability, compares to conventional capsular bag-implanted IOLs. Methods In this clinical study, 42 eyes each of 42 patients who received either a capsular bag-implanted IOL or a Carlevale IOL were followed up. Lens position was determined using anterior segment optical coherence tomography (Anterion; Heidelberg Engineering). Results The mean age of the Carlevale patients was 76.86 +/- 9.08 years, while the mean age of the capsular bag-implanted IOL patients was 68.41 +/- 7.10 years. Scleral-fixated IOLs exhibited a mean decentration of 0.22 +/- 0.02 mm in the horizontal plane and 0.38 +/- 0.04 mm in the vertical plane. In contrast, capsular bag-supported IOLs showed a mean horizontal decentration of 0.18 +/- 0.02 mm and a mean vertical decentration of 0.14 +/- 0.02 mm. The difference in decentration and tilt was statistically significant in the vertical plane ( p 1 < 0.001 and p 2 = 0.002, respectively). In the horizontal plane, there was no statistically significant difference in either decentration or tilt ( p > 0.05). Conclusions Overall, capsular bag-supported IOLs showed less decentration and tilt in the vertical plane than sutureless, scleral-fixated Carlevale IOLs. In the horizontal plane, however, the values are similar.
Today, magnetic resonance imaging (MRI) is considered the diagnostic tool of choice for eye and orbital pathologies. In this article, the MR image characteristics of relevant pathologies are illustrated using case-based examples in the context of clinical findings. Vascular pathologies (such as capillary hemangioma and cavernous venous malformation), inflammatory diseases (such as endocrine orbitopathy), and neoplasms (such as lymphoma, uveal melanoma, retinoblastoma, and ocular/orbital metastasis) are described. Additionally, the role of MRI in acute clinical settings and trauma is discussed. The text explains technical aspects of MRI encompassing field strength and the utilization of receiver coils to optimize image quality and achieve high spatial resolution. Alongside common sequences (T1- and T2-weighted sequences) used in standard anatomic imaging (sAI), the article demonstrates the potential of "multiparametric" imaging techniques (diffusion-weighted imaging, DWI, and dynamic contrast-enhanced imaging, DCE). These innovative MRI sequences depict functional tissue characteristics in addition to morphology alone and thus facilitate radiological assessment.
Herpesvirus infections of the cornea are among the leading infectious causes of corneal vision loss worldwide. Both herpes simplex virus (HSV) and varicella-zoster virus (VZV) play a major role in the development of corneal disease. Following primary infection, both viruses establish lifelong latency in sensory ganglia and may be reactivated by triggering factors such as ultraviolet (UV) exposure, stress, fever, surgery, or immunosuppression. Clinically, ocular herpesvirus infections present with a broad spectrum of manifestations, and early differentiation between these entities is essential for appropriate diagnosis, treatment, and prognosis. HSV keratitis is characterized by a recurrent course and includes epithelial, stromal, endothelial, and neurotrophic forms. Epithelial HSV keratitis results from active viral replication and typically presents as dendritic or geographic keratitis. Non-necrotizing stromal keratitis is predominantly caused by immune-mediated inflammatory responses without significant viral replication, whereas necrotizing stromal keratitis is thought to involve significant viral replication in combination with an excessive immune response. In HSV endotheliitis, both viral and immune-mediated mechanisms play a role. These clinical manifestations may be associated with keratouveitis, secondary glaucoma, iris atrophy, or corneal neovascularization. Recurrent episodes frequently lead to damage of the subbasal corneal nerve plexus, resulting in neurotrophic keratopathy. Varicella-zoster virus may also cause severe ocular complications in patients with herpes zoster ophthalmicus (HZO), including keratitis, uveitis, elevated intraocular pressure, neurotrophic corneal disease, and retinitis. Elderly and immunocompromised individuals are at particularly high risk of severe disease and postherpetic neuralgia. Diagnosis is primarily based on clinical findings and may be supported by corneal esthesiometry, in vivo confocal microscopy, and PCR-based virological testing. Polymerase chain reaction (PCR) analysis of corneal tissue or aqueous humor is particularly valuable in atypical or treatment-resistant cases. Management includes topical and systemic antiviral agents such as acyclovir, valacyclovir, ganciclovir, and famciclovir. Immune-mediated stromal and endothelial keratitis additionally require anti-inflammatory therapy. Neurotrophic forms require regenerative therapies such as autologous serum eye drops, amniotic membrane transplantation, or the recombinant human nerve growth factor cenegermin. Although no licensed vaccine against HSV is currently available, recombinant herpes zoster vaccination provides effective protection against VZV-associated ocular complications.
Dry eye disease (DED) is one of the most common chronic disorders of the ocular surface. It is clinically relevant because it can cause pronounced complaints such as burning, pain, blurred vision, foreign body sensation, photophobia or severe visual disturbance. According to the current pathophysiological understanding, dry eye is a multifactorial, symptomatic disease characterised by a loss of homeostasis of the tear film and/or the ocular surface. Etiologically, tear film instability, hyperosmolarity, inflammatory mechanisms and neurosensory abnormalities play a decisive role. Treating dry eye is one of the most demanding tasks in ophthalmological practice. Patients often present with a high burden of suffering. The multifactorial origin of dry eye calls for a time-intensive, detailed history and differentiated diagnostic work-up. Treatment frequently poses a considerable challenge for the treating physicians and for the affected patients. Current diagnostic and therapeutic recommendations are based on the DEWS III (Dry Eye Workshop III) report of 2025. Therapy no longer follows a stepwise scheme exclusively; instead, an individualised, etiology-oriented, targeted combination therapy is recommended. Particular importance is attached to the recognition of systemic causes, to taking neuropathic pain components into account, and to interdisciplinary collaboration.
