Oligodendrocytes in central nervous system diseases:the effect of cytokine regulation

Cytokines including tumor necrosis factor, interleukins, interferons, and chemokines are abundantly produced in various diseases. As pleiotropic factors, cytokines are involved in nearly every aspect of cellular functions such as migration, survival, proliferation, and differentiation. Oligodendrocytes are the myelin-forming cells in the central nervous system and play critical roles in the conduction of action potentials, supply of metabolic components for axons, and other functions. Emerging evidence suggests that both oligodendrocytes and oligodendrocyte precursor cells are vulnerable to cytokines released under pathological conditions. This review mainly summarizes the effects of cytokines on oligodendrocyte lineage cells in central nervous system diseases. A comprehensive understanding of the effects of cytokines on oligodendrocyte lineage cells contributes to our understanding of central nervous system diseases and offers insights into treatment strategies.

Heterogeneity of mature oligodendrocytes in the central nervous system

Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons.Despite the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is lacking.We delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes.Indeed,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences.Furthermore,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region.Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric disorders.Nevertheless,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations.Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity.Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,hold promise for the development of therapeutic interventions targeting varied central nervous system pathology.

In vivo astrocyte-to-neuron reprogramming for central nervous system regeneration:a narrative review

The inability of damaged neurons to regenerate within the mature central nervous system(CNS)is a significant neuroscientific challenge.Astrocytes are an essential component of the CNS and participate in many physiological processes including blood-brain barrier formation,axon growth regulation,neuronal support,and higher cognitive functions such as memory.Recent reprogramming studies have confirmed that astrocytes in the mature CNS can be transformed into functional neurons.Building on in vitro work,many studies have demonstrated that astrocytes can be transformed into neurons in different disease models to replace damaged or lost cells.However,many findings in this field are controversial,as the source of new neurons has been questioned.This review summarizes progress in reprogramming astrocytes into neurons in vivo in animal models of spinal cord injury,brain injury,Huntington’s disease,Parkinson’s disease,Alzheimer’s disease,and other neurodegenerative conditions.

General anesthetic agents induce neurotoxicity through oligodendrocytes in the developing brain

General anesthetic agents can impact brain function through interactions with neurons and their effects on glial cells.Oligodendrocytes perform essential roles in the central nervous system,including myelin sheath formation,axonal metabolism,and neuroplasticity regulation.They are particularly vulnerable to the effects of general anesthetic agents resulting in impaired proliferation,differentiation,and apoptosis.Neurologists are increasingly interested in the effects of general anesthetic agents on oligodendrocytes.These agents not only act on the surface receptors of oligodendrocytes to elicit neuroinflammation through modulation of signaling pathways,but also disrupt metabolic processes and alter the expression of genes involved in oligodendrocyte development and function.In this review,we summarize the effects of general anesthetic agents on oligodendrocytes.We anticipate that future research will continue to explore these effects and develop strategies to decrease the incidence of adverse reactions associated with the use of general anesthetic agents.

Crosstalk among mitophagy,pyroptosis,ferroptosis,and necroptosis in central nervous system injuries

Central nervous system injuries have a high rate of resulting in disability and mortality;however,at present,effective treatments are lacking.Programmed cell death,which is a genetically determined fo rm of active and ordered cell death with many types,has recently attra cted increasing attention due to its functions in determining the fate of cell survival.A growing number of studies have suggested that programmed cell death is involved in central nervous system injuries and plays an important role in the progression of brain damage.In this review,we provide an ove rview of the role of programmed cell death in central nervous system injuries,including the pathways involved in mitophagy,pyroptosis,ferroptosis,and necroptosis,and the underlying mechanisms by which mitophagy regulates pyroptosis,ferroptosis,and necro ptosis.We also discuss the new direction of therapeutic strategies to rgeting mitophagy for the treatment of central nervous system injuries,with the aim to determine the connection between programmed cell death and central nervous system injuries and to identify new therapies to modulate programmed cell death following central nervous system injury.In conclusion,based on these properties and effects,interventions targeting programmed cell death could be developed as potential therapeutic agents for central nervous system injury patients.

血清Cys-c与NLRP3炎性小体及IL-18的水平对脓毒症AKI患者早期的预测价值

目的探究血清胱抑素C(Cys-c)与核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎性小体及白细胞介素18(IL-18)的血清水平对脓毒症急性肾损伤(AKI)患者早期的预测价值。方法选择42例脓毒症及61例脓毒症AKI作为研究对象,依据Sepsis 3.0及AKI的诊断标准将患者分为脓毒症组及脓毒症AKI组,依次收集2组患者年龄、序贯器官衰竭评估(SOFA)评分、急性生理学与慢性健康状况评分Ⅱ(APACHEⅡ评分)、入住ICU时间、机械通气时间、总住院天数等基本资料,检测和比较2组患者血清中Cys-c、NLRP3炎性小体及IL-18的水平,采用logistic回归探讨脓毒症患者发生AKI的影响因素。用受试者工作特征(ROC)曲线明确血清Cys-c、NLRP3炎性小体及IL-18水平对脓毒症患者发生AKI的预测能力。依据28 d存活与否,将脓毒症AKI患者分为存活组与死亡组,比较2组患者间Cys-c、NLRP3炎性小体及IL-18的水平。结果单因素分析提示脓毒症AKI组患者的血清Cys-c、NLRP3炎性小体及IL-18的水平明显高于脓毒症组(P<0.05),多因素logistic回归分析显示血清Cys-c及NLRP3炎性小体的水平是导致脓毒症患者发生AKI的有害指标。ROC曲线分析,血清Cys-c、NLRP3炎性小体及IL-18的AUC值分别为0.805(95%CI:0.722~0.889)、0.850(95%CI:0.776~0.924)、0.772(95%CI:0.678~0.866),血清Cys-c联合IL-18及NLRP3炎性小体预测脓毒症患者发生AKI的AUC值分别是0.861,0.810,证实血清Cys-c与IL-18的联合预测水平优于单一指标。在存活与死亡组中,死亡组的IL-18水平明显高于存活组(P<0.05)。结论血清Cys-c、NLRP3炎性小体及IL-18的水平对脓毒症AKI患者早期预测具有一定的价值。

Role of CD36 in central nervous system diseases

CD36 is a highly glycosylated integral membrane protein that belongs to the scavenger receptor class B family and regulates the pathological progress of metabolic diseases.CD36 was recently found to be widely expressed in various cell types in the nervous system,including endothelial cells,pericytes,astrocytes,and microglia.CD36 mediates a number of regulatory processes,such as endothelial dysfunction,oxidative stress,mitochondrial dysfunction,and inflammatory responses,which are involved in many central nervous system diseases,such as stroke,Alzheimer’s disease,Parkinson’s disease,and spinal cord injury.CD36 antagonists can suppress CD36 expression or prevent CD36 binding to its ligand,thereby achieving inhibition of CD36-mediated pathways or functions.Here,we reviewed the mechanisms of action of CD36 antagonists,such as Salvianolic acid B,tanshinone IIA,curcumin,sulfosuccinimidyl oleate,antioxidants,and small-molecule compounds.Moreover,we predicted the structures of binding sites between CD36 and antagonists.These sites can provide targets for more efficient and safer CD36 antagonists for the treatment of central nervous system diseases.

Absence of enhancement in a lesion does not preclude primary central nervous system T-cell lymphoma:A case report

BACKGROUND Primary central nervous system lymphoma(PCNSL)is a non-Hodgkin lymphoma that originates in the central nervous system(CNS)and is exclusively limited to the CNS.Although most PCNSLs are diffuse large B-cell lymphomas,primary CNS T-cell lymphomas(PCNSTLs)are rare.PCNSTLs typically demonstrate some degree of enhancement on contrast-enhanced magnetic resonance imaging(MRI).To the best of our knowledge,non-enhancing PCNSTL has not been reported previously.CASE SUMMARY A 69-year-old male presented to the neurology department with complaints of mild cognitive impairment and gradual onset of left lower leg weakness over a span of two weeks.Initial MRI showed asymmetric T2-hyperintense lesions within the brain.No enhancement was observed on the contrast-enhanced T1 image.The initial diagnosis was neuro-Behçet’s disease.Despite high-dose steroid therapy,no alterations in the lesions were identified on initial MRI.The patient’s symptoms deteriorated further.An MRI performed one month after the initial scan revealed an increased lesion extent.Subsequently,brain biopsy confirmed the diagnosis of PCNSTL.The patient underwent definitive combined chemoradiotherapy.However,the patient developed bacteremia and died of septic shock approximately three months after diagnosis.CONCLUSION The absence of enhancement in the lesion did not rule out PCNSTL.A biopsy approach is advisable for pathological confirmation.

CP、Cys-C、RBP及其联合检测在喀什地区维吾尔族慢性肾脏疾病中的诊断价值

目的分析尿外泌体铜蓝蛋白(CP)、血清胱抑素C(Cys-C)、视黄醇结合蛋白(RBP)及其联合检测对喀什地区维吾尔族早期慢性肾脏疾病(CKD)的诊断价值。方法选取2019年1月—2023年1月在新疆喀什地区第一人民医院就诊的225例维吾尔族CKD患者纳入CKD组,另选取同期在体检中心接受健康检查的186例维吾尔族体检者纳入健康对照组。收集两组的尿外泌体CP、血清Cys-C及RBP值。采用logistic回归分析影响早期CKD的因素,绘制受试者工作特征(ROC)曲线分析CP、Cys-C、RBP及其联合检测对早期CKD的临床诊断效能。结果与健康对照组比较,CKD组患者的血清白蛋白、C反应蛋白、血尿素、血沉均明显升高(P<0.05),肾小球滤过率降低(P<0.05)。与健康对照组比较,CKD组尿外泌体CP、血清Cys-C及RBP表达均明显升高(P<0.001)。Logistic回归分析显示,尿外泌体CP、血清Cys-C及RBP是影响早期CKD的独立因素(P<0.001)。ROC曲线分析显示,与尿外泌体CP、血清Cys-C、血清RBP比较,联合检测(并联)诊断早期CKD的AUC、特异度均明显升高。结论早期CKD患者的尿外泌体CP、血清Cys-C、血清RBP均明显升高,尿外泌体CP、血清Cys-C、血清RBP均可用于诊断早期CKD,但联合检测(并联)的诊断效能更高,为尽早诊断CKD提供参考。

Role of copper in central nervous system physiology and pathology

Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central nervous system.Central copper dysregulations have been evidenced in two genetic disorders characterized by mutations in the copper-ATPases ATP7A and ATP7B,Menkes disease and Wilson’s disease,respectively,and also in multifactorial neurological disorders such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,and multiple sclerosis.This review summarizes current knowledge about the role of copper in central nervous system physiology and pathology,reports about unbalances in copper levels and/or distribution under disease,describes relevant animal models for human disorders where copper metabolism genes are dysregulated,and discusses relevant therapeutic approaches modulating copper availability.Overall,alterations in copper metabolism may contribute to the etiology of central nervous system disorders and represent relevant therapeutic targets to restore tissue homeostasis.

Metabolic reprogramming of the inflammatory response in the nervous system:the crossover between inflammation and metabolism

Metabolism is a fundamental process by which biochemicals are broken down to produce energy(catabolism) or used to build macromolecules(anabolism). Metabolism has received renewed attention as a mechanism that generates molecules that modulate multiple cellular responses. This was first identified in cancer cells as the Warburg effect, but it is also present in immunocompetent cells. Studies have revealed a bidirectional influence of cellular metabolism and immune cell function, highlighting the significance of metabolic reprogramming in immune cell activation and effector functions. Metabolic processes such as glycolysis, oxidative phosphorylation, and fatty acid oxidation have been shown to undergo dynamic changes during immune cell response, facilitating the energetic and biosynthetic demands. This review aims to provide a better understanding of the metabolic reprogramming that occurs in different immune cells upon activation, with a special focus on central nervous system disorders. Understanding the metabolic changes of the immune response not only provides insights into the fundamental mechanisms that regulate immune cell function but also opens new approaches for therapeutic strategies aimed at manipulating the immune system.

Annexin A1 in the nervous and ocular systems

The therapeutic potential of Annexin A1,an important member of the Annexin superfamily,has become evident in results of experiments with multiple human systems and animal models.The anti-inflammatory and pro-resolving effects of Annexin A1 are characteristic of pathologies involving the nervous system.In this review,we initially describe the expression sites of Annexin A1,then outline the mechanisms by which Annexin A1 maintains the neurological homeostasis through either formyl peptide receptor 2 or other molecular approaches;and,finally,we discuss the neuroregenerative potential qualities of Annexin A1.The eye and the nervous system are anatomically and functionally connected,but the association between visual system pathogenesis,especially in the retina,and Annexin A1 alterations has not been well summarized.Therefore,we explain the beneficial effects of Annexin A1 for ocular diseases,especially for retinal diseases and glaucoma on the basis of published findings,and we explore present and future delivery strategies for Annexin A1 to the retina.

Meningeal lymphatic vessel crosstalk with central nervous system immune cells in aging and neurodegenerative diseases

Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.

Microglia lactylation in relation to central nervous system diseases

The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.

Lipid droplets in the nervous system:involvement in cell metabolic homeostasis

Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous system.Lipid droplet formation begins with the synthesis of neutral lipids in the endoplasmic reticulum.Previously,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous system.In addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress responses.Furthermore,lipid droplets exhibit specific functions in neurons and glial cells.Dysregulation of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system diseases.This review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and functions.Additionally,it will explore the association between lipid droplets and neurodegenerative disorders.Understanding the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.

High-dose methotrexate and zanubrutinib combination therapy for primary central nervous system lymphoma

In this editorial I comment on the article,published in the current issue of the World Journal of Clinical Oncology.Primary central nervous system lymphoma(PCNSL)is a disease of elderly and immunocompromised patients.The authors reported clinical results of 19 patients with PCNSL treated with zanubrutinib/high dose methotrexate(HD-MTX)until disease progression.They demonstrated that the combination of zanubrutinib with HD-MTX led to a marked clinical response and tolerability among these patients.They also observed that cerebrospinal fluid liquid biopsy to detect circulating tumor DNA may be a good option for evaluating treatment response and tumor burden in patients with PCNSL.PCNSL is a challenging disease for treatment as these patients present with different neurological states and comorbidities.Treatment has evolved over the years from whole brain radiotherapy to HD-MTX followed by autologous stem cell transplant.Gradually,treatment of patients with PCNSL is going to become individualized.

High mobility group box 1 in the central nervous system:regeneration hidden beneath inflammation

High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain injury.Several drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system disorders.Although it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system disorders.In this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory role.Research targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.

血清β2-MG、Cys-C、DKK1联合检测对多发性骨髓瘤患者预后的预测价值

目的:分析多发性骨髓瘤患者血清β2-微球蛋白(β2-MG)、膀抑素C(Cys-C)、Dickkopf-1(DKK1)表达水平及对其预后的预测价值。方法:选取郑州市金水区总医院2019年6月—2023年6月收治的多发性骨髓瘤患者101例为研究组,另选取同期健康体检者76例为对照组。比较2组入院时血清β2-MG、Cys-C、DKK1水平;分析血清β2-MG、Cys-C、DKK1水平与多发性骨髓瘤患者Durie Salmon(D-S)分期、ISS分期的相关性;分析血清β2-MG、Cys-C、DKK1水平联合检测对多发性骨髓瘤患者预后的预测价值。结果:入院时,研究组血清β2-MG、Cys-C、DKK1水平分别为(8.31±0.81)mg/L、(1.71±0.31)mg/L、(8.61±1.86)ng/L,高于对照组的(1.53±0.57)mg/L、(0.72±0.17)mg/L、(2.76±1.41)ng/L,差异均有统计学意义(P<0.05)。D-S分期Ⅲ期多发性骨髓瘤患者血清β2-MG、Cys-C、DKK1水平分别为(8.78±1.88)mg/L、(1.92±0.57)mg/L、(9.13±1.77)ng/L,高于D-S分期Ⅰ~Ⅱ期患者的(7.56±1.57)mg/L、(1.37±0.36)mg/L、(7.78±1.59)ng/L,差异均有统计学意义(P<0.05);ISS分期Ⅲ期多发性骨髓瘤患者血清β2-MG、Cys-C、DKK1水平分别为(9.32±1.67)mg/L、(2.56±0.73)mg/L、(9.33±1.11)ng/L,高于ISS分期Ⅰ~Ⅱ期患者的(7.62±1.54)mg/L、(1.20±0.43)mg/L、(8.12±1.71)ng/L,差异均有统计学意义(P<0.05)。血清β2-MG、Cys-C、DKK1水平与D-S分期、ISS分期均呈正相关(P<0.001)。治疗3个月后,治疗无效组血清β2-MG、Cys-C、DKK1水平高于治疗有效组,差异均有统计学意义(P<0.05)。血清β2-MG、Cys-C、DKK1水平联合检测预测多发性骨髓瘤患者预后的AUC、敏感度、特异度分别为0.822、83.91%、92.86%。结论:多发性骨髓瘤患者血清β2-MG、Cys-C、DKK1处于较高水平,三者联合检测对多发性骨髓瘤患者的预后具有较好的预测价值,可作为判断疗效和预后的血清学指标。

Bruton’s tyrosine kinase inhibitors in primary central nervous system lymphoma:New hopes on the horizon

In this editorial,we comment on the article by Wang et al.This manuscript explores the potential synergistic effects of combining zanubrutinib,a novel oral inhibitor of Bruton’s tyrosine kinase,with high-dose methotrexate(HD-MTX)as a therapeutic intervention for primary central nervous system lymphoma(PCNSL).The study involves a retrospective analysis of 19 PCNSL patients,highlighting clinicopathological characteristics,treatment outcomes,and genomic biomarkers.The results indicate the combination’s good tolerance and strong antitumor activity,with an 84.2%overall response rate.The authors emphasize the potential of zanubrutinib to modulate key genomic features of PCNSL,particularly mutations in myeloid differentiation primary response 88 and cluster of differentiation 79B.Furthermore,the study investigates the role of circulating tumor DNA in cerebrospinal fluid for disease surveillance and treatment response monitoring.In essence,the study provides valuable insights into the potential of combining zanubrutinib with HD-MTX as a frontline therapeutic regimen for PCNSL.The findings underscore the importance of exploring alternative treatment modalities and monitoring genomic and liquid biopsy markers to optimize patient outcomes.While the findings suggest promise,the study’s limitations should be considered,and further research is needed to establish the clinical relevance of this therapeutic approach for PCNSL.

B-scan ultrasound and cytology of the vitreous in primary central nervous system lymphoma with vitreoretinal involvement

AIM: To evaluate the diagnostic value of B-scan ultrasound and explore the cytological characteristics of patients with vitreoretinal lymphoma(VRL) and primary central nervous system lymphoma(PCNSL).METHODS: The clinical data and pathologic specimens from patients with VRL diagnosed at the North Huashan Hospital from 2016 to 2017 were retrospectively reviewed. The patients were diagnosed by slit lamp ophthalmoscopy, B-scan ultrasound, cytology of the vitreous, which was obtained by vitrectomy, and cytokine measurements of interleukin(IL)-10 and IL-6.RESULTS: Twenty-six eyes(19.4%) out of 134 eyes of 67 patients(47 men and 20 women) with PCNSL were diagnosed with VRL by B-scan ultrasound, and 14 eyes(10.4%) were diagnosed by slit lamp ophthalmoscopy. Twenty-four eyes(17.9%) of 17 patients were confirmed as having VRL with cytology. No difference in the association between intracranial lesion location and ocular involvement was found. VRL patients had higher levels of vitreous IL-10 and IL-10/IL-6 when compared with macular hole cases, but the difference was not statistically significant.CONCLUSION: A total of 25.4% of the PCNSL patients had VRL, B-scan ultrasound examination had characteristic features and is recommended over slit lamp ophthalmoscopy for the screening diagnosis of PCNSL with intraocular involvement. Moreover, the cytological and immunohistochemical analyses performed after 25-gauge diagnostic vitrectomy were accurate diagnostic techniques.