Exoscopic removal of the fourth ventricle choroid plexus papilloma with use of a midline suboccipital osteoplastic craniotomy.

Choroid plexus papillomas are relatively rare vascular tumors. In this video, the authors present a pediatric patient who underwent exoscopic removal of the fourth ventricle choroid plexus papilloma with the use of a midline suboccipital osteoplastic craniotomy. The exoscope in the fourth ventricle lesion helps to improve visualization in all directions, with the surgeon being able to maintain a comfortable position throughout the procedure. In addition, the midline suboccipital osteoplastic craniotomy helps to reduce the potential risks of complications, in particular, CSF leak and craniovertebral junction instability. The video can be found here: https://stream.cadmore.media/r10.3171/2023.10.FOCVID23106.

Bipolar, high-voltage, long-duration pulsed radiofrequency ablation of the Gasserian ganglion for the treatment of trigeminal neuralgia in a patient with a cardiac implantable electronic device: illustrative case.

BACKGROUND: One of the common methods of treating trigeminal neuralgia (TN) nowadays is radiofrequency therapy. However, it has serious limitations in patients with a cardiac pacemaker because of electromagnetic interference. Therefore, it is crucial to select optimal radiofrequency ablation parameters to make this procedure safe with favorable outcomes for such patients. OBSERVATIONS: In this study, the authors present a case of a 70-year-old man with a history of cardiac pacemaker dependency and previous microvascular decompression with complaints of severe, constant facial pain. After reprogramming the cardiac implantable electronic device (CIED), the authors performed bipolar, high-voltage, long-duration pulsed radiofrequency therapy (PRFT) of the Gasserian ganglion under electrocardiography and pulse rate control in the pre-, intra-, and postoperative periods. There were no cardiovascular or neurological complications after PRFT. The patient reported relief of pain after the procedure, and at the 9-month follow-up, he was pain-free. LESSONS: This clinical case demonstrates that the use of bipolar, high-voltage PRFT for TN treatment in patients with a CIED can be safe and effective, provided that the rules and pacemaker instructions are followed. It is necessary to use ablative treatment with caution and to guide the patient in collaboration with a cardiac surgeon and an anesthesiologist resuscitator.

Modified orbitozygomatic craniotomy with a single burr hole in the alternative sphenoid ridge keyhole.

BACKGROUND: One-piece modified orbitozygomatic approach (OZA) is an extended version of the pterional approach that also includes orbital walls and frontal process of the zygomatic bone. For this craniotomy one burr hole must be placed in MacCarty keyhole and another - in the temporal region. OBJECTIVE: To develop a technique of the one-piece modified OZA with single a burr hole in the alternative sphenoid ridge keyhole that allows access to orbit, anterior cranial fossa and middle cranial fossa and apply it intraoperatively. METHODS: A single human head specimen was used. The dissection was performed using standard surgical instruments high-speed Stryker drill. Every stage of the approach was photographed. We also report a surgical case of a patient with orbital cavernous hemangioma that was resected using the described technique. RESULTS: The technique of the one-piece modified OZA with a single burr hole in the alternative sphenoid ridge keyhole is described, and its advantages and limitations are analyzed. The technique is used to totally resect an orbital cavernous hemangioma with good functional and cosmetic result. CONCLUSION: Modified OZA with a single burr hole in the sphenoid ridge keyhole is possible and may be an alternative to the classic technique. The advantages of this variation are the placement of just one burr hole and the preservation of a larger portion of the orbital roof. The latter facilitates better bone reconstruction and better cosmetic outcome. Disadvantages are the difficulty of identifying the location of the sphenoid ridge keyhole and risk of damaging the dura.

Anatomical Justification of Extradural Resection of the Anterior Clinoid Process.

Objective The study aimed to provide neuroanatomical justification of the extradural resection of the anterior clinoid process (ACP). Material and Method Using a cross-sectional study design, 47 cranial computed tomography (CT) scans were examined. There were 31 (65.96%) females aged 28 to 79 years. The measured dimensions were ACP length and width, and optic strut (OS) width. Index (i acp ) was measured as the ratio of ACP width to ACP length. The ACP volume and working operating field (WOF) volume were measured using Syngo.via Siemens program. The percentage expansion of WOF after removal of the ACP was estimated on 5 fixed human cadaver heads with the exoscope VITOM 3D. The possibilities of the combined approach were demonstrated in a clinical case. Results The mean ACP lengths were 11.31 ± 2.76 and 11.54 ± 2.86 mm, on the right and left, respectively. The mean ACP widths were 7.70 ± 1.66 and 7.64 ± 1.67 mm, on the right and left, respectively. Average i acp was 0.67 (minimum 0.45; maximum 0.90). The width of the OS varied in the range from 1.37 to 4.75 mm. The average volume of right ACP was 0.71 ± 0.16 cm 3 , right WOF was 3.26 ± 0.74 cm 3 , left ACP was 0.71 ± 0.15 cm 3 , left and WOF was 3.20 ± 0.76 cm 3 . Removal of the right ACP expanded the right WOF by 22.21 ± 3.88%, and left ACP by 22.78 ± 5.50%. There was an approximately 25% increase in the WOF from the cadaveric dissections. Taking into account the variability of the ACP and OS, we proposed our own surgical classification of complicated (i acp ≥ 0.67; medium OS 2.5 mm ≤ 4.0 mm; wide OS ≥ 4.0 mm; ACP with pneumatization) and uncomplicated ACP (i acp 0.45 ≤ 0.67 mm; i acp ≤ 0.45; narrow OS ≤ 2.5 mm; ACP without pneumatization). Using this classification, we developed an algorithm for ACP dissection and removal. This was piloted in a clinical case of microsurgical clipping of a left internal carotid artery-posterior communicating artery aneurysm via the left minipterional approach. Conclusion Extradural removal of ACP expands the WOF by approximately 25%, it helps neurosurgeons to improve proximal vascular control and avoid complications, and expands the range of indications for neurosurgical interventions in the skull base area.

Purely endoscopic biportal and monoportal removal of the choroid plexus papilloma of the third ventricle with bilateral spread to the lateral ventricles.

Modern neuroendoscopy makes it possible to treat tumors of various localizations with a reduced risk of intra- and postoperative complications. In this video, the authors present biportal and monoportal techniques for the removal of the choroid plexus papilloma of the third ventricle with bilateral spread to the lateral ventricles in a 1-year-old boy. For this operation, they successfully used a new instrument for neuroendoscopy, LigaSure, specially designed for intra-abdominal surgery. The video can be found here: https://stream.cadmore.media/r10.3171/2023.1.FOCVID22170.

p62/SQSTM1 indirectly mediates remote multipotent mesenchymal cells and rescues bone loss and bone marrow integrity in ovariectomized rats.

Intramuscular administration of p62/SQSTM1 (sequestosome1)-encoding plasmid demonstrated an anticancer effect in rodent models and dogs as well as a high safety profile and the first evidence of clinical benefits in humans. Also, an anti-inflammatory effect of the plasmid was reported in several rodent disease models. Yet, the mechanisms of action for the p62 plasmid remain unknown. Here, we tested a hypothesis that the p62-plasmid can act through the modulation of bone marrow multipotent mesenchymal cells (MSCs). We demonstrated that a p62 plasmid can affect MSCs indirectly by stimulating p62-transfected cells to secrete an active ingredient(s) sensed by untransfected MSCs. When we transfected MSCs with the p62-plasmid, collected their supernatant, and added it to an untransfected MSCs culture, it switched the differentiation state and prompt osteogenic responses of the untransfected MSCs. According to an accepted viewpoint, ovariectomy leads to bone pathology via dysregulation of MSCs, and restoring the MSC homeostasis would restore ovariectomy-induced bone damage. To validate our in vitro observations in a clinically relevant in vivo model, we administered the p62 plasmid to ovariectomized rats. It partially reversed bone loss and notably reduced adipogenesis with concurrent reestablishing of the MSC subpopulation pool within the bone marrow. Overall, our study suggests that remote modulation of progenitor MSCs via administering a p62-encoding plasmid may constitute a mechanism for its previously reported effects and presents a feasible disease-preventing and/or therapeutic strategy.

P62/SQSTM1 beyond Autophagy: Physiological Role and Therapeutic Applications in Laboratory and Domestic Animals.

Inflammation is the preceding condition for the development of mild and severe pathological conditions, including various forms of osteopenia, cancer, metabolic syndromes, neurological disorders, atherosclerosis, cardiovascular, lung diseases, etc., in human and animals. The inflammatory status is induced by multifarious intracellular signaling cascades, where cytokines, chemokines, arachidonic acid metabolites, adhesion molecules, immune cells and other components foster a "slow burn" at a local or systemic level. Assuming that countering inflammation limits the development of inflammation-based diseases, a series of new side-effects-free therapies was assessed in experimental and domestic animals. Within the targets of the drug candidates for quenching inflammation, an archetypal autophagic gear, the p62/sqstm1 protein, has currently earned attention from researchers. Intracellular p62 has been recently coined as a multi-task tool associated with autophagy, bone remodeling, bone marrow integrity, cancer progression, and the maintenance of systemic homeostasis. Accordingly, p62 can act as an effective suppressor of inflamm-aging, reducing oxidative stress and proinflammatory signals. Such an operational schedule renders this protein an effective watchdog for degenerative diseases and cancer development in laboratory and pet animals. This review summarizes the current findings concerning p62 activities as a molecular hub for cell and tissues metabolism and in a variety of inflammatory diseases and other pathological conditions. It also specifically addresses the applications of exogenous p62 (DNA plasmid) as an anti-inflammatory and homeostatic regulator in the treatment of osteoporosis, metabolic syndrome, age-related macular degeneration and cancer in animals, and the possible application of p62 plasmid in other inflammation-associated diseases.

P62/SQSTM1 enhances osteogenesis and attenuates inflammatory signals in bone marrow microenvironment.

Bone marrow-derived mesenchymal/stromal stem cells (MSCs) became a major focus of research since the anti-inflammatory features and the osteogenic commitment of these cells can prevent the inflamm-aging and various form of osteopenia in humans and animals. We previously showed that p62/SQSTM1 plasmid can prompt release of anti-inflammatory cytokines/chemokines by MSC when injected in adult mice. Furthermore, it can enhance osteoblastogenesis at the expense of adipogenesis and ameliorate bone density and bone remodeling. On the other hand, absence of p62 partially exhausted MSC pool caused expansion of fat cells within bone marrow and pro-inflammatory mediator's accumulation. Given the critical function of p62 as molecular hub of MSC dynamics, here, using MSCs from p62 knockout adult mice, we investigated the effect of this protein on MSC survival and bone-forming molecule cascades. We found that the main osteogenic routes are impaired in absence of p62. In particular, lack of p62 can suppress Smads activation, and Osterix and CREBs expression, thus significantly modifying the schedule of MSCs differentiation. MSCs obtained from p62-/- mice have also demonstrate an amplified NFκB/ Smad1/5/8 colocalization along with NFκB activation in the nucleus, which precludes Smads binding to target promoters. Considering the "teamwork" of TGFß, PTH and BMP2 on MSC homeostatic behavior, we consider that p62 exerts an essential role as a hub protein. Lastly, ex vivo pulsing p62-deficient MSCs, which then will be administered to a patient as a cell therapy, may be considered as a treatment for bone and bone marrow disorders.

Microsurgical Resection of Intracanalicular Vestibular Schwannoma via Retrosigmoid Approach: 3-Dimensional Operative Video.

Vestibular schwannomas are a multifaceted group of tumors that can present with different sizes and involvement of critical neurovascular structures.1-6 While operating on these tumors, a critical goal is postoperative preservation of facial nerve function and hearing. We present the case of a 66-year-old male with a history of severe left-sided tinnitus and progressive hearing loss (Video 1). Preoperative imaging depicted a lesion highly suggestive of an intracanalicular vestibular schwannoma. Due to worsening of symptoms and after thoughtful discussion with the patient, microsurgical resection was indicated under constant neurophysiologic monitoring. A retrosigmoid approach was employed, and the posterior wall of the internal auditory canal was opened, allowing exposure of tumor and its total resection. Postoperative imaging demonstrated complete tumor resection. The patient's symptoms improve, and there were no new neurologic deficits on follow-up. Anatomical images were a Courtesy of the Rhoton Collection, American Association of Neurological Surgeons (AANS)/Neurosurgical Research and Education Foundation (NREF).

Microsurgical treatment of symptomatic vestibular schwannomas in patients under 40: different results before and after age of 30.

In 10-15% of cases of vestibular schwannoma (VS), age at diagnosis is 40 years or less. Little is known about the differences in natural history, surgical findings, and postoperative outcomes of such younger patients as compared to those of greater age. To analyze clinical and surgical and imaging data of a consecutive series of n = 50 patients with unilateral sporadic VS, aged 40 years or younger - separated in a very young group (15-30 years) and a moderately young group (31-40 years). Retrospective case series. Fifty consecutive patients under 40 years of age underwent microsurgical resection of unilateral sporadic VS via the retrosigmoid approach. The study cohort was subdivided into two groups according to the age range: group A, age range 15-30 years (n = 23 patients), and group B, age range 31-40 years (n = 27 patients). The adherence of VS capsule to surrounding nervous structures and the tendency of the tumors to bleed were evaluated by reviewing video records; the course of the FN in relation to the tumor's surface was assessed in each case. Microsurgical removal of tumor was classified as total (T), near total (residual tumor volume < 5%), subtotal (residual tumor volume 5-10%), or partial (residual tumor volume > 10%). Mean tumor size of entire cohort was 2.53 (range: 0.6-5.8) cm: 2.84 cm in group A and 2.36 cm in group B (p = NS). Facial nerve course and position within the cerebellopontine angle did not differ significantly between the two groups. At 6-month follow-up, FN functional outcome was HBI-II in 69.5% in group A, versus 96.3% in group B (p < .001). Hearing preservation was achieved in 60.0% of patients of group A and in 58.3% of group B (p = NS). Total and near-total resection was feasible in 95.6% of cases of group A and in 88.9% of group B (p = NS). Tumor capsule was tightly adherent to nervous structures in 69.6% patients of group A and in 22.2% of group B (p < .05). Significant bleeding was encountered in 56.5% of group A tumors, and in 29.6% of group B tumors (p < .01). Microsurgery of VS in patients aged 40 or less is associated with good functional results, and with high rates of total and near total tumor removal. Patients < 30 years of age have more adherent tumor capsules. Furthermore, their tumors exhibit a tendency to larger sizes, to hypervascularization, to profuse intraoperative bleeding and they present worse long-term functional FN results when compared to patients in their fourth decade of life. Our limited experience seems to suggest that a near total resection in very young VS patients with large tumors should be preferred in adherent and hypervascularized cases, in order to maximize resection and preserve function.

Endoscopic Treatment of Middle Cranial Fossa Arachnoid Cysts in Children: Surgical Results of 65 Cases.

OBJECTIVE: Congenital arachnoid cysts in the middle fossa accounts for 50% of all intracranial arachnoid cysts. Several management options have been described; however, no single technique has been universally adopted. We describe a series of pediatric patients with middle cranial fossa arachnoid cyst that were treated through an innovative minimally invasive endoscopic technique, along with their clinical aspects and surgical outcomes. METHODS: Data from 65 patients operated between 2012 and 2018 were retrospectively analyzed. Follow-up ranged from 12 to 96 months. Clinical presentation and surgical outcomes were collected. Endoscopic cystocisternostomy was performed in all patients using a mini endoscope. RESULTS: There were 41 male and 24 female patients, with a mean age of 5.3 years at the time of treatment. Except for 4 patients, all presented with 1 or more symptoms, and the most frequent were intracranial hypertension signs. All patients were treated with the same surgical technique, with an efficacy of 81.5%. CONCLUSIONS: Using a mini endoscope allow us to perform multiple fenestrations along the arachnoid and deeply inspect the basal cisterns, achieving a much wider communication between the cyst and subarachnoid space with a high success rate and minimal invasiveness.

Microsurgical Resection of Trigeminal Schwannoma via Anterior Petrosal Approach: 2-Dimensional Operative Video.

Trigeminal schwannomas are complex lesions that may be related to many critical neurovascular structures. We present the case of a 59-year-old male presenting a history of left-sided trigeminal neuralgia. Preoperative imaging demonstrated a mass highly suggestive of a trigeminal schwannoma, and microsurgical resection was indicated considering the progressive symptomatology and important mass effect (Video 1). A middle fossa route including an anterior petrosectomy was chosen. The patient was placed supine with the head rotated to the contralateral side, and an arcuate incision was performed. A V-shaped zygomatic osteotomy was done to mobilize the temporalis muscle more inferiorly and better expose the middle fossa floor. Following craniotomy, peeling of the dura propria from the lateral wall of cavernous sinus was carried out starting by coagulation of middle meningeal artery. Some tumor was already identified and removed, and then the anterior petrosectomy was performed until we exposed the posterior fossa dura. The middle fossa dural incision was connected with the other one at the posterior fossa dura, by coagulation of the superior petrosal sinus. The tentorium was completely cut toward the incisura. After lesion debulking, the tumor was progressively removed by peeling the arachnoid from the lesion to maintain arachnoid planes and preserve the nerves and their blood supply. Postoperative imaging demonstrated complete tumor resection. The patient's symptoms improved, and there were no neurologic deficits on follow-up. Extensive laboratory training is fundamental to be familiarized with the normal anatomic nuances and prepared to face the anatomy distorted by lesion. Informed consent was obtained from the patient for the procedure and publication of this operative video.

Extreme Lateral Supracerebellar Infratentorial Approach: Surgical Anatomy and Review of the Literature.

OBJECTIVE: The extreme lateral supracerebellar infratentorial (ELSI) approach has the potential to access several distinct anatomical regions that are otherwise difficult to reach. We have illustrated the surgical anatomy through cadaveric dissections and provided an extensive review of the literature to highlight the versatility of this approach, its limits, and comparisons with alternative approaches. METHODS: The surgical anatomy of the ELSI has been described using 1 adult-injected cadaveric head. Formalized noninjected brain specimens were also dissected to describe the brain parenchymal anatomy of the region. An extensive review of the literature was performed according to each targeted anatomical region. Illustrative cases are also presented. RESULTS: The ELSI approach allows for wide exposure of the middle and posterolateral incisural spaces with direct access to centrally located intra-axial structures such as the splenium, pulvinar, brainstem, and mesial temporal lobe. In addition, for skull base extra-axial tumors such as petroclival meningiomas, the ELSI approach represents a rapid and adequate method of access without the use of extensive skull base approaches. CONCLUSIONS: The ELSI approach represents one of the most versatile approaches with respect to its ability to address several anatomical regions centered at the posterior and middle incisural spaces. For intra-axial pathologies, the approach allows for access to the central core of the brain with several advantages compared with alternate approaches that frequently involve significant brain retraction and cortical incisions. In specific cases of skull base lesions, the ELSI approach is an elegant alternative to traditionally used skull base approaches, thereby avoiding approach-related morbidity.

Response of a chemo-resistant triple-negative breast cancer patient to a combination of p62-encoding plasmid, Elenagen, and CMF chemotherapy.

Triple-negative breast cancers are often characterized by aggressive behavior and short clinical course once they become chemotherapy-resistant. We describe below a patient who has shown a response to combination of chemotherapy with Elenagen, a plasmid encoding p62. Elenagen was tested in a previous phase I/II study in patients with refractory solid tumors and shown to be safe. Also, plasmid ability to halt tumor progression and restore sensitivity to chemotherapy was found. Preclinical data supports effects on tumor grade and change the tumor's microenvironment in spontaneous canine breast cancers. We describe here a 48-year old female with triple-negative and BRCA1/2-negative breast cancer who had a primary resistance to chemotherapy and negative dynamics despite the use of multiple lines of treatments. Elenagen was applied intramuscularly at a dose of 1 mg weekly in combination with standard chemotherapy scheme CMF (cyclophosphamide, methotrexate, fluorouracil). In this patient we observed partial tumor regression (by 33%) and 19 weeks of progression-free survival. This first observed objective response to a combination of Elenagen with chemotherapy demonstrates that even in heavily pretreated chemo-resistant triple-negative tumor, the addition of Elenagen to a chemotherapy regimen can cause an objective response and increase in progression-free survival. Such a regimen is worthy of further study in a larger number of patients.

Endoscopic Interhemispheric Disconnection for Intractable Multifocal Epilepsy: Surgical Technique and Functional Neuroanatomy.

BACKGROUND: Callosotomy represents a palliative procedure for intractable multifocal epilepsy. The extent of callosotomy and the benefits of adding anterior and posterior commissurotomy are debated. OBJECTIVE: To describe a new technique of a purely endoscopic procedure to disconnect the corpus callosum, the anterior, posterior, and habenular commissures through the use of a single burr hole via a transfrontal transventricular route. METHODS: Our surgical series was retrospectively reviewed in terms of seizure control (Engel's class) and complication rate. Five cadaveric specimens were used to demonstrate the surgical anatomy of commissural fibers and third ventricle. RESULTS: The procedure may be divided into 3 steps: (1) endoscopic transventricular transforaminal anterior commissure disconnection; (2) disconnection of posterior and habenular commissures; and (3) total callosotomy. Fifty-seven patients were included in the analysis. A favorable outcome in terms of epilepsy control (Engel class 1 to 3) was found in 71.4% of patients undergoing callosotomy coupled with anterior, posterior, and habenular commissure disconnection against 53% of patients with isolated callosotomy (P = .26). Patients with drop attacks had better epilepsy outcome independently from the surgical procedure used. CONCLUSION: The full endoscopic callosotomy coupled with disconnection of anterior, posterior and habenular commissures is a safe alternative to treat multifocal refractory epilepsy. A gain in seizure outcome might be present in this cohort of patients treated with total interhemispheric disconnection when compared with isolated callosotomy. Larger studies are required to confirm these findings.

Microsurgical Resection of a Middle Cerebellar Peduncle Cavernous Malformation: 3-Dimensional Operative Video.

Brainstem cavernous malformations are frequently surrounded by vital structures, which often makes surgical treatment a challenging task even to the most skilled surgeon. Accordingly, microsurgical excision is preferably offered to symptomatic patients and superficial lesions.1-3 We present the case of a 41-yr-old male presenting with progressive dizziness and diplopia. Neurological examination showed horizontal nystagmus, dysmetria, and unbalance. Preoperative magnetic resonance imaging (MRI) suggested a cavernous malformation in the right middle cerebellar peduncle. A telovelar approach was employed with the guidance of intraoperative neurophysiological monitoring. An exophytic lesion was identified in the right middle cerebellar peduncle and a clear cleavage plane was obtained allowing circumferential dissection around the capsule. The lesion was removed en bloc. Postoperative MRI confirmed a complete excision of the malformation. The patient presented an improvement in his initial symptoms, with no new neurological deficit. Cavernous malformations related with the fourth ventricle can be successfully resected through a telovelar approach in select cases, especially when exophytic, where the surgeon might take advantage of the path created by the lesion. Informed consent was obtained from the patient for the procedure and publication of this operative video. Anatomic images were a courtesy of the Rhoton Collection, American Association of Neurological Surgeons (AANS)/Neurosurgical Research and Education Foundation (NREF).

p62-DNA-encoding plasmid reverts tumor grade, changes tumor stroma, and enhances anticancer immunity.

Previously, we reported that the administration of a p62/SQSTM1-encoding plasmid demonstrates high safety and signs of clinical benefits for human cancer patients. The treatment also suppressed tumor growth and metastasis in dogs and mouse models. Here we investigated some mechanistic aspects of these effects. In mammary tumors bearing-dogs, i.m. injections of p62 plasmid reduced tumor sizes and their aggressive potential in 5 out of 6 animals, with one carcinoma switching to adenoma. The treatment increased levels of smooth muscle actin in stroma cells and type III collagen in the extracellular matrix, which correlate with a good clinical prognosis. The p62 treatment also increased the abundance of intratumoral T-cells. Because of the role of adaptive immunity cannot be tested in dogs, we compared the protective effects of the p62 plasmid against B16 melanoma in wild type C57BL/6J mice versus their SCID counterpart lacking lymphocytes. The plasmid was only protective in the wild type strain. Also, p62 plasmid amplified the anti-tumor effect of T-cell transfer from tumor-bearing animals to animals challenged with the same tumors. We conclude that the plasmid acts via re-modeling of the tumor microenvironment, making it more favorable for increased anti-cancer immunity. Thus, the p62-encoding plasmid might be a new adjuvant for cancer treatments.

p62 /SQSTM1 coding plasmid prevents age related macular degeneration in a rat model.

P62/SQSTM1, a multi-domain protein that regulates inflammation, apoptosis, and autophagy, has been linked to age-related pathologies. For example, previously we demonstrated that administration of p62/SQSTM1-encoding plasmid reduced chronic inflammation and alleviated osteoporosis and metabolic syndrome in animal models. Herein, we built upon these findings to investigate effect of the p62-encoding plasmid on an age-related macular degeneration (AMD), a progressive neurodegenerative ocular disease, using spontaneous retinopathy in senescence-accelerated OXYS rats as a model. Overall, the p62DNA decreased the incidence and severity of retinopathy. In retinal pigment epithelium (RPE), p62DNA administration slowed down development of the destructive alterations of RPE cells, including loss of regular hexagonal shape, hypertrophy, and multinucleation. In neuroretina, p62DNA prevented gliosis, retinal thinning, and significantly inhibited microglia/macrophages migration to the outer retina, prohibiting their subretinal accumulation. Taken together, our results suggest that the p62DNA has a strong retinoprotective effect in AMD.